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Validated All-in-One™ qPCR Primer for CDKN2A(NM_000077.5) Search again
Product ID:
HQP151410
(click here to view gene annotation page)
Powered by BiozSpecies:
Human
Symbol:
Alias:
ARF, CAI2, CDK4I, CDKN2, CMM2, INK4, INK4A, MLM, MTS-1, MTS1, P14, P14ARF, P16, P16-INK4A, P16INK4, P16INK4A, P19, P19ARF, TP16
Gene Description:
cyclin dependent kinase inhibitor 2A
Target Gene Accession:
NM_000077.5(click here to view gene page)
Estimated Delivery:
Approximately 1-3 weeks, but may vary. Please email sales@genecopoeia.com or call 301-762-0888 to confirm ETA.
Important Note:
By default, qPCR primer pairs are designed to measure the expression level of the splice variant (accession number) you selected for this gene WITHOUT consideration of other possible variants of this gene. If this gene has multiple variants, and you would like to measure the expression levels of one particular variant, multiple variants, or all variants, please contact us for a custom service project at inquiry@genecopoeia.com.
Validated result:
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| A | B |
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Each All-in-One™ qPCR Primer is experimentally validated to yield a single dissociation curve peak and to generate a single amplification of the correct size for the targeted gene. A cDNA Pool, containing reverse transcript products of 8 different human tissue total RNA(Liver, Testis,Muscle,Thyroid,Brain,Spleen,Stomach,Small Intestine)),was used as the qPCR validation template. qPCR was performed using 0.2 µM primer with 2XAll-in-One™ qPCR Mix (Catalog#: QP001,QP002,QP004,QP005). Reactions were incubated for 10min. at 95°C, followed by 40 cycles of 95°C for 10 sec.; 60°C, 20 sec. and 72°C, 15sec. using Bio-Rad iQ5™ Instrument. At the end of the last cycle, temperature was increased from 72 to 95°C to produce a melting curve. Panel A: Validated Result for Amplification Curve; Panel B: Validated Result for Melting Curve. |
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Summary
This gene generates several transcript variants which differ in their first exons. At least three alternatively spliced variants encoding distinct proteins have been reported, two of which encode structurally related isoforms known to function as inhibitors of CDK4 kinase. The remaining transcript includes an alternate first exon located 20 Kb upstream of the remainder of the gene; this transcript contains an alternate open reading frame (ARF) that specifies a protein which is structurally unrelated to the products of the other variants. This ARF product functions as a stabilizer of the tumor suppressor protein p53 as it can interact with, and sequester, MDM1, a protein responsible for the degradation of p53. In spite of the structural and functional differences, the CDK inhibitor isoforms and the ARF product encoded by this gene, through the regulatory roles of CDK4 and p53 in cell cycle G1 progression, share a common functionality in cell cycle G1 control. This gene is frequently mutated or deleted in a wide variety of tumors, and is known to be an important tumor suppressor gene. [provided by RefSeq].
Gene References into function
- penetrance of mutations causing melanoma modified by MC1R genotype
- expression is related to apoptosis in thymus
- A method of detecting deletions in the INK4A gene is described in detail.
- p16INK4a reversibly inhibited cell growth. CDKIs mediate growth arrest in human osteosarcoma cell lines and provides further evidence of the existence of molecular links between cellular mortality and immortality.
- inhibits Plasmodium falciparum cyclin dependent protein kinases
- Up-regulated p16 expression may represent a unique feature of aggressive neuroblastoma.
- protein interaction mapping with Hdm2
- p16(INK4a) lesions are common, early abnormalities that undergo clonal expansion in Barrett's metaplastic epithelium
- The mutation creates a false GT splice donor site 105 bases 5' of exon 3 and has been demonstrated to result in aberrant splicing of the mRNA.
- In the ovarian cancer cell lines studied, cell growth was inhibited after transfection with p16(INK4a), p21(WAF1/Cip-1), and p53.
- P16 gene silencing by hypermethylation is more common in null cell adenomas. The role of p16 in the pathogenesis of pituitary adenomas is restricted to specific tumor subtypes.
- Aberrations of the p14(ARF) and p16(INK4a) genes in renal cell carcinomas
- p16 protein was up-regulated in A549 cells treated with ATRA.
- inactivation may not play an important role in the malignant transformation of ependymomas
- Study suggested that p16 overexpression might play a role in the development and progression of pituitary adenomas.
- Homozygous deletion of ink4A is associated with poor survival in primary central nervous system lymphoma patients
- The percentage of families with two melanoma cases/family harboring a mutation was low (7%, 2/27), but rose to 45% (9/20) if one of the melanoma patients carried multiple melanomas or if pancreatic cancer was present in that family.
- Analysis of the p16 gene status of non-familial dysplastic nevus syndrome patients.
- p14(ARF) nuclear overexpression in aggressive B-cell lymphomas is a sensor of malfunction of the common tumor suppressor pathways.
- Expression of wild-type p16(INK4a) and p53 genes in K562 cells results in reduced proliferation and apoptosis. Co-transfection with both genes significantly inhibited cell proliferation when compared to transfection with either p16(INK4a) or p53 gene.
- Down-regulated p16 expression predicts poor prognosis in patients with extrahepatic biliary tract carcinomas
- increased nucleolar expression of p14ARF and an absence of nucleolar or nucleoplasmic p14ARF/Hdm2 complexes in Reed Sternberg cells in Hodgkin's lymphoma
- distinct methylation pattern in bladder cancer with frequent methylation of RARbeta, DAPK, E-cadherin, and p16.
- role in progession of mycosis fungoides
- Transgenic expression leads to enhanced apoptosis and differentiation arrest of immature thymocytes
- Losses of INK4a/INK4b gene products play a big role in meningioma formation & malignant progression. Inactivation of p16/p15 and pl4ARF pendent pathways possibly along with telomerase activation might be critical for meningioma immortalization.
- Human tumor suppressor ARF impedes S-phase progression independent of p53.
- There was a statistically significant association between p16 gene deletion and early stage, well differentiated bladder transitional cell carcinoma.
- Abnormal expression of p16 gene then becomes involved in the development and metastasis of breast cancer.
- Frequent abnormalities of the p16 gene in mycosis fungoides and sezary syndrome. polymorphisms promoter methylation
- ARF promoter is regulated by E2F through both direct binding to the promoter sequences and indirectly, probably by being tethered to the ARF promoter by Sp1-like factors.
- Overexpression of p16INK4a can be used as an early marker of cervical cancer
- p16/INK4a gene inactivation by hypermethylation is associated with aggressive variants of monoclonal gammopathies.
- loss of P16 protein by promoter methylation results in non small cell lung tumorigenesis
- Alterations in genetic and epigenetic status of p14ARF is associated with osteosarcoma growth
- Results indicate that p14ARF aberrant promoter methylation could be involved in bladder carcinogenesis and that plasma DNA is a potential prognostic marker in urinary bladder cancer.
- Cirrhotic livers reveal genetic changes in the MDM2-P14ARF system of cell cycle regulators.
- Glutathione S-transferase P1 and NADPH quinone oxidoreductase polymorphisms are associated with aberrant promoter methylation of P16(INK4a) and O(6)-methylguanine-DNA methyltransferase in sputum.
- Activation of caspase-3 and cleavage of Rb are associated with p16-mediated apoptosis in human non-small cell lung cancer cells.
- Genetic status of cell cycle regulators in squamous cell carcinoma of the oesophagus: the CDKN2A (p16(INK4a) and p14(ARF) ) and p53 genes are major targets for inactivation
- Inactivation of p16/CDKN2 and p15/MTS2 is associated with prognosis and response to chemotherapy in ovarian cancer.
- Aberrant methylation of the p16 gene may be a useful indicator of the potential malignancy of epithelial cells of the pancreas.
- The N-terminal half of p16 is significantly more sensitive to proteolysis in both tumor-derived mutant proteins than in the wild type, suggesting that stabilization of the N-terminal region could be a useful strategy for future therapeutic development.
- downregulation by Id-1 expression
- Deletion analysis of p16(INKa) and p15(INKb) in relapsed childhood acute lymphoblastic leukemia.
- Tumor suppressor gene p16 and Rb expression in gastric cardia precancerous lesions from subjects at a high incidence area in northern China.
- Inactivation of tumor suppressor genes p15(INK4b) and p16(INK4a) in primary cutaneous B cell lymphoma.
- Results show that in human fibroblasts, ARF is not induced demonstrably by RAS, pointing to significant differences between the proliferative barriers implemented by the CDKN2A locus in different cell types or species.
- mutations in melanoma
- geographical variation in the penetrance of mutations for melanoma
- expression at different stages of bladder cancer
- A two-stage, p16(INK4A)- and p53-dependent keratinocyte senescence mechanism that limits replicative potential independent of telomere status.
- p14(ARF) down-regulates E2F-dependent transcription. In cells undergoing E2F-dependent apoptosis it arrests the cell cycle. p14(ARF) has multiple binding domains for E2F-1, one within the N-terminal region coinciding with the regulation of E2F activity.
- promoter methylation studied in 80 patients with head and neck squamous cell carcinoma (HNSCC)
- Adenovirus-mediated overexpression of p14(ARF) induces p53 and Bax-independent apoptosis.
- Human p14(ARF)-mediated cell cycle arrest strictly depends on intact p53 signaling pathways.
- Multiple interacting domains contribute to p14ARF mediated inhibition of MDM2
- The t(8;21) fusion protein, AML1 ETO, specifically represses the transcription of the p14(ARF) tumor suppressor in acute myeloid leukemia.
- regulates cell cycle
- Promoter hypermethylation and the 540 C>T polymorphism of CDKN2A in cutaneous melanoma of the vertical growth phase. (P = 0.025). Point mutations in CDKN2A were found in 4%; 90% had loss of heterozygosity at one or more of 4 markers.
- aberrant CDKN2A promoter methylation is associated with preinvasive bronchial lesions in lung carcinoma
- Prognostic significance of p16INK4a alterations and 9p21 loss of heterozygosity in locally advanced laryngeal squamous cell carcinoma.
- Loss of heterozygosity of p16 correlates with minimal residual disease at the end of the induction therapy in non-high risk childhood B-cell precursor acute lymphoblastic leukemia. LOH of p16 may be a marker of chemotherapy resistance in BCP-ALL.
- ATM and the ARF-p53 tumor suppressor pathway may cooperate in the pathogenesis of diffuse large B-cell lymphoma
- Inactivation of p21WAF1 sensitizes cells to apoptosis via an increase of both p14ARF and p53 levels and an alteration of the Bax/Bcl-2 ratio
- Differential p16 patterns by interphase cytogenetics in malignant peripheral nerve sheath tumor and morphologically similar spindle cell neoplasms.
- cooperates with CARF in activating p53
- Genetic alterations of INK4alpha/ARF locus and p53 are observed in human hepatocellular carcinoma.
- MYCL1, FHIT, SPARC, p16(INK4) and TP53 genes associated to lung cancer in idiopathic pulmonary fibrosis
- an important role for p16 gene in the cell cycle regulation of multiple myeloma tumor cells
- role of p14ARF in breast cancer cell sensitivity to cisplatin
- Deletions in the CDKN2A locus and hypermethylation in the CDKN2A promoter region play a role in ovarian granulosa cell tumorogenesis.
- Gene expression modulated by hnRNP A1 and hnRNP A2 RNA binding proteins
- Systemic processes may affect this region of 9p21 at times during melanoma progression.
- p14ARF promotes accumulation of (H)Mdm2 conjugated to the small ubiquitin-like protein SUMO-1
- deletion predicts relapse in children with ALL treated according to the Nordic protocols NOPHO-86 and NOPHO-92
- Ink4a-Arf deficiency allows for GBM formation from astrocytes and that it enhances tumor incidence in neural progenitor cells.
- Sensor of morphological changes and of short-lived perturbations in cell cycle and in nucleolar function.
- p16INK4a promoter mutations are frequent in primary sclerosing cholangitis (PSC) and PSC-associated cholangiocarcinoma.
- mutations in sporadic and familial melanoma in the Polish population
- degree expression is related to the histological type of tumor but not to the histological indicators of tumor invasiveness and that intragenic mutations and promoter hypermethylation are not major mechanisms of p16 inactivation in sporadic uveal melanom
- c-MET and INK4a/ARF, situated at the nexus of pathways regulating myogenic growth and differentiation, represent critical targets in rhabdomyosarcoma pathogenesis
- Methylation of p16 was for the first time observed in retinoblastoma (9 tumors, 17%).
- Data suggest that p16INK4a plays a principal role in Ras-induced growth arrest in human fibroblasts.
- The consistency of p16 protein deletion in different stages of nasopharyngeal carcinoma (NPC) suggests that the deletion of p16 protein is an early event in the development of NPC.
- p16(INK4a) inactivation is not required to immortalize primary human mammary epithelial cells.
- Findings indicate correlation between the increased expression of p16 during the progression of skin from actinic keratosis to in situ squamous cell carcinoma to invasive squamous cell carcinoma.
- Ink4a/arf plays a critical role in UV-induced melanomagenesis.
- association of p14ARF with the p120E4F transcriptional repressor enhances cell cycle inhibition
- These data provide further evidence for a pancreatic cancer-melanoma syndrome associated with CDKN2A germline mutations affecting p16.
- No association was found between p16 expression and host phenotype but loss of p16 staining was associated with thicker lesions and a high mitotic index. In the progression of sporadic primary melanomas, p16 loss may be associated with aggressive tumours
- Histopathological features of cutaneous malignant melanomas from families with mutations in the CDKN2A gene are described.
- No mutations of the CDKN2A tumour suppressor gene were detected among patients with melanoma and additional cancers.
- Our data suggest that Bmi-1 extends the replicative life span of human fibroblasts by suppressing the p16-dependent senescence pathway.
- Keratinocytes of chronic psoriatic plaques were characterized by enhanced p16, p14(ARF), and p12 expression accompanied by elevated Egr-1 levels
- inactivation of both p16(INK4a) and pRb is associated with immortalization of human cells including fibroblasts and epithelial cells and telomerase-positive cells and ALT-positive cells
- analyzed the methylation status of the promoter region of the CDKN2A gene in gastric adenocarcinomas; CDKN2A promoter methylation was not significantly associated with microsatellite instability
- p16INK4A is phosphorylated upon Cdk4 association
- There may be a role for 3' UTR polymorphisms in the CDKN2A gene in tumor invasiveness.
- Hereditary p16-Leiden mutation in a patient with multiple head and neck tumors
- p16 Hypermethylation in the early stage of hepatitis B virus-associated hepatocarcinogenesis.
- Pathogenetic and biologic significance of TP14ARF alterations in nonsmall cell lung carcinoma.
- observations suggest that p14ARF tumor suppressor activity may be linked to its oligomerization status and sensitive to the redox status of the cell
- Activation of ERK together with its downstream transcriptional machinery mediated p16(INK4a) expression that led to HepG2 growth inhibition triggered by TPA and Saikosaponin a.
- Methylation of INK4a is associated with the development of malignant pancreatic disease
- study indicated that p16 expression was reduced in adenoid cystic carcinoma cases of higher histological grade of malignancy and that hypermethylation of its promoter gene may be involved in its process in some cases
- Hypermethylation changes in exon 1 and exon 2 of p16 gene. Homozygous deletion frequency of exon 1 and exon 2 of p16 gene was 20 % and 10 %, respectively. No mutation found in exon 1 of p16 gene. Abnormal single strands found in 2 cases in exon 2.
- Frequencies of LOH in two microsatellite sites, D9s171 and D9s1604, in p16 genome were associated with development of gastric cancer. No correlation between LOH frequency and cell differentiated types of tumor cells or clinical stages.
- induces G2 arrest and apoptosis independently of p53 leading to regression of tumours established in nude mice
- Abolition of p21(Cip1/Waf1) and p16(Ink4a) functions prevented oncogenically activated Ras from inducing growth arrest and was sufficient for limited anchorage-independent growth but not tumorigenesis.
- Epithelial cells with methylation of p16 promoter sequences occur in focal patches of histologically normal mammary tissue of a substantial fraction of healthy, cancer-free women.
- The exon 2 region was required for physical binding of p14(ARF) to Topo I & stimulatory activity. p14(ARF) (R71A) was more efficient than wild-type to activate Topo I. Nucleolar location is linked the biological function of the ARF-Topo I complex.
- Inactivation of p14ARF and p16INK4a genes by either homozygous deletion or promoter hypermethylation may be important for the molecular pathogenesis of salivary malignant tumors
- Methylation inactivation of P16 is associated with oral cancer
- Inhibitor shows antitumor effect on glioma cells
- p16(INK4a) was up-regulated at the invasive front of the majority of basal cell carcinomas with infiltrative growth patterns, followed by ceased proliferation.
- close correlation between inactivation of p16 gene and gastric carcinoma
- Promoter methylation of p16INK4a is associated with biliary disease
- Over-expressed in squamous cell carcinoma of the mouth.
- cells from patients with diabetic nephritis exhibit significantly lower protein and mRNA expression of p16.
- p53 contributes to a delayed form of senescence that requires telomere shortening, in p16-deficient melanocytes. These findings provide some basis for the role of p16 in melanoma susceptibility.
- p16(INK4a) plays a role in maintaining homeostasis during erythroid differentiation.
- Flavopiridol in low, clinically achievable concentrations may have significant cytostatic effects, particularly in p16- melanoma cells, and may provide new molecular-based therapies for melanoma, particularly when combined with anti-apoptotic agents.
- high frequency of NRAS codon 61 mutations detected in primary hereditary melanomas may be the result of a hypermutability phenotype associated with a hereditary predisposition for melanoma development in patients with germline CDKN2A mutations
- Hypermethylation of the CDKN2A gene is associated with colorectal cancer
- diffuse, strong positivity with p16 protein suggests an endocervical rather than an endometrial origin of an adenocarcinoma
- p16 promoter hypermethylation is associated with gastric cancer patients
- frequent inactivation of the p14ARF and p16INK4a genes may be an important mechanism for the dysfunction of p53 and Rb growth regulatory pathways during bladder cancer development.
- EBV LMP1 blocks p16INK4 pathway by promoting nuclear export of E2F-4 and E2F-5.
- Results identify the point during neoplastic progression in epithelia when the tumor suppressor p16 and laminin 5 are expressed and suggest that normal epithelia may use the same mechanism to generate non-dividing, motile cells for wound repair.
- No significant differences between ocular melanoma cases and controls in the frequency of any of the four most common variants of CDKN2A, and no melanoma case carried a deleterious germline CDKN2A mutation.
- the anti-cancer effect of p16 is modulated by p16-mediated cell cycle arrest and by the induction of senescence
- P16 gene alteration may be associated with the development of some type of cervix neoplasms.
- Aberrant p16 promoter methylation is associated with smokers and former smokers with nonsmall cell lung cancer
- alterations of the INK4a-ARF locus are frequent and important events not only in the carcinogenesis of malignant, but also in benign tumors.
- hypermethylation of the p16INK4A promotor region is a frequent and an early event during thyroid carcinogenesis and is associated with tumor progression and dedifferentiation
- inactivation of p16INK4a/retinoblastoma pathway results in cell division in hepatocellular carcinoma through overexpression of Id-1
- CDKN2A polymorphism is a potential indicator of melanoma predisposition among first-degree relatives of patients with malignant melanoma.
- p16INK4 methylation causes gene silencing in primary colorectal carcinomas
- In a mixed uveal and cutaneous melanoma family, CDKN2A is demonstrated for the first time to be a uveal melanoma (UM)susceptibility gene, loss of function of which is involved in the pathogenesis of UM.
- splice site mutations do predispose to disease in a subset of melanoma-prone kindreds
- Tumor suppressor genes p15(INK4b), p14(ARF) and p16(INK4a) are located at the 9p21 locus in 26 cryopreserved neurofibromatosis type 1-related malignant peripheral nerve sheath tumors.
- E2a-Pbx1 and Bmi-1 are likely to play a role in the pathogenesis of human lymphoid leukemias through downregulation of the INK4A-ARF gene
- Tumor suppressor p16INK4a determines sensitivity of human cells to transformation
- Our study suggested that mutation/hypermethylation/allelic alterations (LOH/MA) of CDKN2A were associated with the development of dysplastic head and neck lesions.
- In colorectal tumors, nuclear expression of beta-catenin, p16 and c-myc was quantitatively increased from normal mucosa to premalignant adenoma, primary carcinoma and lymph node metastatic carcinoma.
- the p16(INK4a)/pRb pathway mediates hSNF5-induced cellular senescence
- Results reveal a molecular mechanism of ARF in regulating ribosome biogenesis and cell proliferation via inhibiting B23.
- CDKN2A L94Q mutation may have a role in familial malignant melanoma
- a significant minority of pancreatic intraepithelial lesions arising in patients with chronic pancreatitis show loss of p16 expression
- involvement of p14(ARF) in the development of pancreatic cancer
- P16INK4a emerged with the most consistent correlations with age and histologic changes and inversely correlated with cell replication in kidney aging
- p16INK4a and Fhit expression is altered in carcinogenesis and progression of human oral cancer
- Deletions of p16INK4a gene are uncommon and loss of p16 protein expression is a common event in melanoma
- p16 inactivation by promoter methylation has different effects in non-small cell lung and colorectal cancer: clinical implications
- P16INK4 is required for human fibroblast senescence and for limiting ras-induced epithelial cell proliferation as evidenced from siRNA-directed "knock down."
- Upregulation of p14ARF paralleled with MDM2 inhibition contributes to p53 accumulation in the nucleus in radiation-treated breast cancer cells.
- INK4a and ARF may be repressed by Bmi-1 protein in a pathway leading to human colorectal carcinogenesis
- Mutations and intragenic allelic losses in CDKN2A appear to play a role in the development of esophageal squamous cell carcinoma in high-risk Chinese populations.
- INK4a-ARF mutations are infrequent outside stringent familial criteria, and germline INK4a-ARF deletions are rarely involved in genetic predisposition to melanoma
- Downregulation of p16(INK4a) and loss of wild-type p53 expression occurs after escape from cell immortalization
- v-Fos-stimulated invasion is independent of the pRb/p16(INK4a) and p53 tumor suppressor pathways and telomerase
- Results suggest that p53 degradation and inhibition of p14(ARF) signaling are independent functions of HPV16 E6, and that long-term proliferation of mammary epithelial cells requires inactivation of the p14(ARF)-p53 pathway.
- No p16 gene mutations were found in any cases of oropharngeal squamous cell carcinoma in this study.
- p16-Leiden germline mutation may be involved in susceptibility to lung cancer and oral squamous cell carcinomas development in some patients
- CDKN2A inactivation played a significant role in the development of squamous cell carcinoma of the larynx
- p16INK4A gene plays an important role in the pathogenesis of hepatocellular carcinoma.
- Alteration of p16 gene alone or in combination with alterations of other tumor suppressor genes on chromosome 9p is a prognostic indicator in gallbladder carcinoma.
- Methylation of the p16 gene CpG island ia common to all three histological patterns associated with Cushing's disease.
- the expression of DAP kinase, p19ARF, p53, and p21WAF1 was significantly down-regulated in the chronically HIV-1SF2-infected HUT78 T cells
- In human colon cancer cell lines,the expression of the p16(INK4A) gene is regulated by DNA methylation.
- p16INK4A, p14ARF, p53, and PCNA have roles in the progression of cervical neoplasia
- CDKN2A plays an important role in laryngeal squamous cell carcinoma development and progression
- p21(Waf1) can activate the transcription of p16(INK4); this effect is GC-box dependent; and the transcription factor Sp1 plays a key role in this event
- Results describe the significance of p16INK4A and p15INK5B transcription suppression with hypermethylation of their genes' 5'CpG islands during human hepatocellular carcinogenesis.
- E47 is involved in the regulation of p16(INK4a) transcription in cellular senescence
- for both p16(INK4a) and p14(ARF), promoter methylation is the commonest mechanism of gene inactivation.
- relationships between familial melanoma, pancreatic cancer and germline CDKN2A mutations using published data to determine whether any identifiable patterns exist
- Together, a melanoma-predisposing gene (identified as CDKN2A in melanoma-prone families), number of nevi and/or dysplastic nevi, and sun-related covariates influence melanoma risk in both families unselected by family history and melanoma-prone families.
- Alteration of the p14(ARF)gene may play a role in early stage Japanese hepatocellular carcinoma carcinogenesis. .
- p14ARF contributes to the p53 DNA damage response following ionizing irradiation.
- The inactivation of the tumor suppressor gene p16 plays a role in the carcinogenesis of squamous cell carcinomas of the oral cavity, the pharynx and the larynx. There is no influence on the tumor dependent prognosis.
- ARF attenuates c-Myc independently of the ARF-p53 axis
- Induction of p14(ARF) increased resistance to the folate antagonists. Depletion of thymidine in the medium reversed this resistance, indicating that p14(ARF) induction increases the reliance of these cells on thymidine salvage.
- We observed p16 (INK4A) immunolocalization in both the nucleus and the cytoplasm of a proportion of tumor cells
- evidence that p16(INK4a) is degraded by N-terminal ubiquitination in a cell density-dependent manner
- E-cadherin and p16INK4a are commonly methylated in non-small cell lung cancer
- In invasive urothelial carcinomas, the p16-pRb pathway, the p14(ARF)-p53 pathway, or both pathways were altered or not activated and were thus involved in invasive bladder tumorigenesis.
- p14ARF-induced inhibition of MCF7 cell proliferation was significantly attenuated by downregulation of ATM by RNAi.
- The combination of low expression of TS and induction of p16(INK4a) after chemotherapy can be important indicators of the sensitivity to 5-FU-based chemotherapy in colorectal cancers.
- ARF interacts with MDM2 in the nucleoplasm but is consequently subject to proteasomal degradation
- A significant increase in p16(INK4A) and Bax expression was found in ulccerative colitis-associated tumors.
- p16 methylation may have a role in the malignant transformation of gastric dysplasia
- In melanocytic lesions, p16INK4A and NF-kappaB p65 expression were inversely correlated with levels of the nuclear component of NF-kappaB p65.
- accumulation of nevi in mutation carriers supports a nevogenic role for this CDKN2A mutation.
- only one germline CDKN2A mutation with functional significance, which was an exon 1 missense mutation resulting in a proline-to-leucine substitution in codon 48
- expression in malignant melanomas with or without a contiguous nevus remnant
- Inactivation of p16INK4a as a critical event for overcoming telomere-independent crisis, immortalizing MRC5 fibroblasts and overcoming ras-induced premature senescence.
- Data show that p16 is frequently expressed in squamous carcinoma of the cervix, vagina and vulva, but is not seen in cases of benign and low grade lesions.
- Following transfection of the ribozyme construct in pancreatic cancer cells, mutant p16 mRNA molecules were repaired and p16 protein synthesis restored.
- ability to promote SUMO conjugation is a general property of the p14 Arf tumor suppressor
- a role for the p14ARF-Topo I complex in rRNA transcription and/or maturation.
- ARF can inhibit c-Myc by a unique and direct mechanism that is independent of p53
- p16 mutations were found in 50% of pancreatic adenocarcinoma cell lines and 75% of primary tumors. They were mostly missense/deletion/frameshift mutations in exon 2.
- review of p15INK4b, p14ARF and p16INK4a function as cell cycle inhibitors where they are involved in the inhibition of G1 phase progression, and promoter methylation in hematologic malignancies and solid tumors
- alterations in both p53 and p16ink4a can contribute to recessive dystrophic epidermolysis bullosa-associated squamous cell carcinoma
- demonstrate genetically the oncogenic cooperation between defects on INK4a/ARF and p27, which are common alterations in human cancer
- p16(INK4A) as a highly specific marker of CIN and HR-HPV type, but expression of this protein does not seem to be of any prognostic value in cervical cancer or in predicting the clearance of HR-HPV after treatment
- the RASSF1A but not p16INK4a methylated promoter region has a role in progression of non-small cell lung cancer
- overexpression of p16INK4a and p73 may be involved in breast cancer and associated with poor tumor characteristics
- Frequent p16INK4a promoter hypermethylation is associated with human papillomavirus-infected female lung cancer
- Loss of p16-related cell cycle regulation may be associated with the development of Epstein-Barr virus-related gastric carcinoma.
- nucleophosmin in the nucleolus, ARF utilizes an additional mechanism of tumor suppression, one that is readily antagonized by Mdm2
- MDM2-p73-P14ARF pathway is involved in the progression of bladder cancer to a more malignant and aggressive form.
- Aberrant expression of pRb and p16, alone and in combination, heralds poor prognosis in patients with CRC.
- Different mechanisms of CDKN2A deletion prevail in different human cancers.
- overexpression of p16INK4A and p14ARF act as potential biomarkers for cervical cancer progression from premalignant lesions.
- p16-Rb pathway plans important role in tumor progression and prognosis in vertical growth phase melanomas
- p16INK4A hypermethylation has a role in hepatocarcinogenesis from an early stage
- CDKN2A mutation is associated with melanoma
- in tumor cells lacking functional p53 and/or p21, p14(ARF) impaired mitotic entry and enforced a primarily cytoplasmic localization of p34(cdc2) that was associated with a decrease in p34(cdc2) kinase activity and reduced p34(cdc2) protein expression
- Simultaneous measurement of p16 and L-ras mutations provides an additional tool in differential diagnosis of chronic pancreatitis and pancreatic adenocarcinoma.
- p16(INK4a) contributes to the p53-independent response to telomere damage.
- MITF regulates p16INK4A expression in melanocytes.
- frequent p14 gene abnormalities (90%) and inactivation (40-60%) was in striking contrast to the same pathological subtype of systemic lymphoma, suggesting a difference in carcinogenesis between PCNSL and systemic lymphoma.
- Mutation of p16 and Rb genes might be correlated with progression of gallbladder carcinoma
- senescence induced by the forced expression of p16 in early passage IMR90 fibroblasts or osteosarcoma U2OS cells was accompanied by expression of the two most acidic p16 variants
- AP-1 heterodimers may contribute to the regulation of ARF expression upon oncogenic signaling
- Loss of p16 protein is associated with gastrointestinal stromal tumors
- p14ARF induces p53-dependent cell cycle arrest but not apoptosis
- Point mutations in CDKNA2 are uncommon event in the atypical nevi of persons with melanoma.
- Signaling events required for G1 cell cycle arrest and apoptosis induction by p14 ARF dissociate upstream of p53.
- P16INK4A protein plays a significant role in the formation of benign neoplasms and their malignant counterparts derived from follicular thyroid cell.
- ARF induces the ATR- and Chk1-dependent phosphorylation of the RelA transactivation domain at threonine 505, a site required for ARF-dependent repression of RelA transcriptional activity.
- Hypermethylation and protein expression of p16 INK4A is associated with uterine cervical lesions
- p16 was lacking in the malignant rhabdoid tumor of the liver.
- p16(INK4A) reconstitution in p16(INK4A)-deficient T-ALL cells induced cell cycle arrest in the presence of cyclin E and c-Myc expression, uncoupled growth from cell cycle progression and caused a sequential process of growth, differentiation and apoptosi
- low p16 expression due to methylation may contribute to tumor enlargement and expansion of colorectal cancer
- p16 facilitates the movement of band 3 to plasma membrane with increased anion transport activity in 293t cells
- Inacativaton of this cell cycle regulatory genes by DNA methylation could be associated with tumorigenesis in NK cell disorders.
- TP53, CDKN1A, CDKN2A, and CDKN2B have roles in tumorigenesis in skin melanomas, but none of them is a main mutation target for melanoma tumorigenesis
- Hypermethylation of p16, RUNX3, and HPP1 in Barreett exophagus may represent independent risk factors for the progression of Barrett esophagus to esophageal cancer.
- Results demonstrated concordant loss of p16 proteiin and MTAP expression in pancreatic intraepithelial neoplasia.
- The p14ARF transcript is clearly important in disease predisposition in a subset of melanoma pedigrees.
- aberrant methylation of p16 was observed in all of the stages, confirming that this epigenetic alteration is an early event during gastric carcinogenesis.
- p14ARF acts through a common modification of diverse binding partners, including Ubc9
- The Aberrant expression of Cyclin-Dependent Kinase Inhibitor p16 were determined in bone marrow samples of children with de novo B-lineage (n=170) and T-lineage (n=25) acute lymphoblastic leukemia (ALL).
- CDKN2A appears to be a low penetrance breast cancer susceptibility gene in Poland
- Increased expression of senescence-associated cell cycle inhibitor p16INK4a is associated with deteriorating renal transplants and diseased native kidney
- chromobox homolog 7 represses p16Ink4a and p14Arf expression in normal and tumor-derived prostate cells, affecting their growth
- whereas wild type p16INK4a strongly inhibits NF-kappaB transcriptional activity, a subset of melanoma-associated p16INK4a mutants show reduced NF-kappaB inhibitory function
- Use of p16INKra immunocytochemistry can improve the prognostic statement in routine procedure for patients with cervical intraepithelial neoplasia.
- PKCalpha is specifically required for TPA-induced ERK(MAPK) signaling to trigger gene expressions of p15(INK4b) and p16(INK4a) leading to HepG2 growth inhibition
- Data show that in patients with squamous cell carcinoma of the tongue, p14(ARF) expression predicts for improved survival independent of established prognostic markers.
- data reinforce the hypothesis that ARF is a melanoma susceptibility gene
- These findings confirm that loss of p16 function could be involved in pancreatic cancer and may explain at least in part the aggressive behaviour of this tumor type.
- All HPV-positive and -negative cervical cancer cell lines expressed p16(INK4A) protein, and that indicates the existence of dysplasia or malignancy in the uterine cervix, regardless of HPV infection.
- Exogenous P16 has negative effects on the malignant proliferation of the bladder cancer cells, and it may be considered as target for potential anticancer drugs.
- Results suggest that CDKN2A may be haploinsufficient in human cancer.
- A delay in p16INK4a induction and an extended lifespan of human keratinocytes when grown in co-culture with post-mitotic fibroblast feeder cells were identified.
- Binding of ARF to DP1 results in an inhibition of the interaction between DP1 and E2F1 and the G1 arrest.
- the p14ARF-p53-MDM2 pathway has a role in development of oral squamous cell carcinoma
- cytoplasmic p16 bound cyclin dependent kinase (cdk)4/6, potentially indicating that p16 could have a function in the cytoplasm
- Arf is haploinsufficient for the induction of acute myeloid leukemia in the presence of the inv(16)
- p34(SEI-1) and p16(INK4A) have different roles in development of squamous cell carcinoma of the head and neck
- p16INK4a, RARbeta, and MGMT expression is activated by genistein and related soy isoflavones partially through a direct inhibition of DNA methyltransferase
- regulation of p14(ARF) gene by E2F is distinct from that of classical E2F targets; results indicate that the distinct regulation constitutes the basis of p14(ARF) function as a tumor suppressor
- The frequency of p16INK4A or CDH13 hypermethylation in patient serum and the total lack of methylation in serum from healthy individuals, offer a promising tool for non invasive early detection of lung cancer.
- CDKN2A mutation carriers in the general population have a much lower risk of melanoma than that suggested by estimates obtained from multiple-case families. Familial clustering of melanoma occurs without identifiable mutations in CDKN2A.
- In summary, the p53/p21 pathway is mainly responsible for GC-induced apoptosis, but the coordinated activation of the p53/p21 and p16 pathway is responsible for GC-induced endothelial cell senescence through a Rb-dependent mechanism.
- results demonstrate that early onset of senescence in omentum-derived human peritoneal mesothelial cells may be associated with oxidative stress-induced upregulation of p16INK4a
- Methylation in the p16 promoter region is biologically significant, being associated with phosphorylation of pRb and cell growth in human hepatocellular carcinoma cells
- p16INK4a expression in cervical preneoplastic and neoplastic lesions and correlation with lesion grade
- Expression of p16 was associated with better overall survival.
- hSNF5 binds the p16INK4a and p21CIP/WAF1 promoters, suggesting that it directly regulates transcription of these genes.
- INK4A was expressed in cervical intraepithelial neoplasms, but not in the normal uterine cervix.
- Age does not appear to be a major indicator of CDKN2A or CDK4 mutations in melanoma patients in Spain
- This is the first study indicating that MSP analysis of p16(INK4a) and p14(ARF) genes is a useful biomarker for the pathological stage, clinical outcome, and prognosis of patients with bladder cancer.
- methylation of the INK4A/ARF locus is not a disease-specific molecular change in mononuclear cell fraction; the p14ARF and p16INK4A genes are differentially methylated
- Overexpression of p16INK4a is induced by the human papillomavirus oncoprotein E7 and distinguishes dysplastic lesions from benign changes.
- Effect of mutation on nevus distribution.
- Methylation of p16INK4a may contribute to the malignant progression of gastric MALT lymphomas.
- Three CDKN2A mutations (3/20; 15%), including one novel nonsense mutation (Trp110Stop) and two Arg24Pro missense alterations were found.
- study shows that p14ARF directly associates with Myc and relocates Myc from the nucleoplasm to the nucleolus, in addition, p14ARF down regulates Myc activated transcription
- genetic alterations of p16 gene are rare events in patients with CLL; Sequencing of these cases revealed the presence of the ALA148THR polymorphism. Methylation analysis of p16 gene promoter revealed hypermethylation of CpG islands in 6/34 cases (17.6%).
- Findings confirmed that p16 overexpression is associated to high-grade precancerous lesions and cervical carcinomas, and demonstrated that immunohistochemical evaluation of p16 may be a useful biomarker in identifying HR-HPV-infected low-grade lesions.
- tumor protein p53 mutations and p16(INK4A) promoter methylation, but not alterations in the H-Ras and K-Ras genes, might be involved in the malignant progression of pleomorphic adenomas into carcinoma
- data demonstrated p16 promoter methylation in a highly tumour specific pattern in oral squamous cell carcinoma
- Demonstration of centrosome dysfunction in cells due to loss of p16(INK4a) suggests that, under the appropriate conditions, these cells can become aneuploid
- The expression of p16 was significantly higher in tumorous tissues than in non-tumorous ones. A significant relationship was observed between p53 and COX-2, or p16 and COX-2. But no obvious correlation was seen between p53 and p16 expressions.
- Controls the retinoblastoma protein pathway to trigger its antiproliferative function.
- human cytomegalovirus(HCMV)infection stimulates the expression of p16(INK4a); evidence provided that p16(INK4a) upregulation plays a positive role for HCMV replication
- tobacco smoking may be associated with an increased incidence of aberrant promoter methylation of the p16 and MGMT genes in non-small cell lung cancer
- A moderate overexpression of p14(ARF) with a normal expression of p16(INK4a) was observed in imatinib-resistant patients with chronic myeloid leukemia
- p16(INK4a) expression was regulated by the Polycomb group repressor Bmi-1, which is shown as a direct transcriptional target of c-Myc.
- p16 hypermethylation may be a frequent genetic aberration in multiple myeloma.
- Nine patients had p16 mutations within the Barrett's epithelium.
- aberrant expression of Cdc6 is oncogenic by directly repressing the INK4/ARF locus through the RD(INK4/ARF) element
- results suggest that p16 suppresses MMP-2 by blocking Sp1-mediated gene transcription
- These results demonstrate that the MAPK ERK signaling pathway contributes to the p53-independent antiproliferative functions of p14ARF. Furthermore, they identify a new mechanism by which phosphorylation at serine 216 participates to Cdc25C inactivation.
- The A148T variant of the CDKN2A gene is not associated with melanoma risk in the French and Italian populations.
- The cytoplasmic immunoreactivity of p16 appears to be an unfavorable prognostic indicator in high-grade astrocytoma patients.
- Differences in oncoprotein expression between endometriotic and adenomyotic tissues provide further evidence that the pathogenesis of endometriosis is different from that of adenomyosis.
- Genomic alterations by fine-mapping MLPA were validated at the DNA level for CDKN2A in head and neck squamous cell carcinoma; exon 1-alpha(p16INK4a) was identified as the smallest region of loss.
- determination that p16 is not activated in hTERT immortalization of urothelial cells
- Hypermethylation of p14(ARF) is associated with primary adenocarcinomas of the small bowel
- Results show that p14/ARF is frequently involved in primitive neuroectodermal tumour (PNET) carcinogenesis, with a higher frequency, supratentorial PNET than for Medulloblastoma.
- results support a model in which the nucleolus serves as a p53 upstream sensor of cellular stress, and add to a growing body of evidence that nucleolar sequestration of ARF prevents activation of p53
- results suggest that p16 is up-regulated or accumulated in small cell carcinomas (SmCCs) of the uterine cervix, probably caused by infection with human papillomavirus; p14 inactivation is of high prevalence in SmCCs
- results suggest that p16INK4a overexpression is independent of human papillomavirus infection in lobular endocervical glandular hyperplasia
- in head and neck squamous cell carcinoma low dietary intake of folate is associated with p16(INK4A) methylation, and this relationship is modified by the methylene tetrahydrofolate reductase genotype
- Persistent hepatitis B infection may be associated with high rate of p16 methylation, and involved in development of hepatocellular carcinoma.
- This study suggests that simultaneous hypermethylation of both p16INK4a and p14ARF genes is greater prognostic value in sporadic human colorectal cancer.
- the molecular basis of the ARF-B23 interaction
- it is concluded that mutation of p53 & deletion of p16 might play important roles in the tumorigenesis of gliomas
- These genetic and translational observations establish a cooperative role of Pten and Ink4a/Arf in the development of HS and provide mechanistic insights into the pathogenesis of human HS.
- The high frequency of methylation of the CDKN2A gene promoter suggests that the inactivation of tumor suppressor genes and of the genes related to the control of cellular proliferation through this mechanism is involved in gallbladder carcinogenesis.
- The activation of ATM/ATR/CHK signaling pathways contributes to this G2 checkpoint and highlight the interrelated roles of p14ARF and the Tip60 protein in the initiation of this DNA damage-signaling cascade.
- laminin 5 and p16INK4A have roles in wound healing and senescence
- p16INK4a regulates keratinocyte clonal evolution and that inactivation of p16INK4a in epidermal stem cells is necessary for maintaining stemness.
- In 50 of the 66 primitive colorectal tumor cases at least one significant alteration was identified in Ki-Ras and/or TP53 and/or p16(INK4A) genes.
- p16(ink4a) plays a role in the radiation resistance of chondrosarcoma cell lines and suggests that restoring p16 expression will improve the radiation sensitivity of human chondrosarcomas.
- a causal role of p16(INK4A) disruption in modulating DNA hypermethylation, and identify a dynamic and active process whereby epigenetic modulation of gene expression is activated as an early event in breast tumor progression
- p16(INK4a)/Rb-induced telomere-independent senescence
- p16INK4a gene silencing during CIN was not determined to be a particularly rare event; however, it does not correlate with either HPV status or CIN grading.
- p16 and p14ARF have roles in radio- and chemosensitivity of malignant gliomas
- Aberrant promoter hypermethylation of p16 gene is associated with oral squamous cell carcinomas
- Because p16(INK4a)-positive cells were detected only in premalignant lesions and carcinomas but not in normal or benign tissues, p16(INK4a) may aid in the diagnosis of PIN and prostate cancer in difficult cases.
- Decreased expression of p16 in dysplastic lesions, as found in this study, may reflect the biologic events involving loss of p16 gene function in the pathogenesis of oral cancer.
- Transfer of the p16(INK4a) and p18(INK4c) genes and CDK4I suppressed the production of MMP-3 and MCP-1.
- p16 is induced as an "emergency brake" in cells experiencing sustained replicative stress within regenerative epithelial crypts in ulcerative colitis
- aberrant methylation of p16(INK4a) is seen in in chromate workers with lung cancer
- A better understanding of ARF's nucleolar interactions could further elucidate the regulation of the p53 pathway and suggest new therapeutic approaches to restore p53 function.
- Induction of p16(INK4A) mediated by nuclear beta-catenin and p21(WAF1), along with loss of pRb expression, may be important for initial steps during trans-differentiation of Em Ca cells.
- p53 is functional in the absence of p14(ARF) in malignant pleural mesothelioma
- The patients with emphysema had significantly higher percentages of type II cells positive for p16INK4a and p21CIP1/WAF1/Sdi1 than the asymptomatic smokers and nonsmokers.
- novel germline mutation in exon 1 of the CDKN2A gene, E27X, which we first detected in melanoma patients living in or originally from a small geographic area bordering Liguria in north-western Italy
- CDKN2A germ-line mutations is associated with cutaneous malignant melanoma
- Wip1 overexpression abrogates the homeostatic balance maintained through the p38-p53-Wip1 pathway, and contributes to malignant progression by inactivating wild-type p53 and p38 MAPK as well as decreasing p16 protein levels in human breast tissues.
- The variation in CDKN2A mutations is consistent with the lower melanoma incidence rates in Europe and higher rates of sporadic melanoma in Australia.
- Homozygous CDKN2A/p14(ARF)/CDKN2B deletion plays an important role in pleomorphic xanthoastrocytoma.
- high-risk human papillomaviruses were involved in inducing p16 and hTERT overexpression in Bowenoid papulosis
- Upon p14ARF overexpression, UBF was found hypophosphorylated, thus unable to efficiently recruit the transcription complex, these data define a new p53-independent pathway that could regulate cell cycle through the negative control of rRNA transcription.
- Percentage of cases with p16 staining decreased significantly with increasing degree of dysplasia of aerodigestive tract
- p16 is expressed in cutaneous squamous cell carcinomas
- Study is the first to report a large CDKN2A germline deletion with a breakpoint located within an exon.
- The variable expression levels of cell-cycle inhibitor genes CDKN2A, CDKN2B, and CDKN1B due to regulatory polymorphisms could indeed influence the risk of childhood pre-B ALL and contribute to carcinogenesis.
- Expression of DNMT3B was inversely correlated with that of p14ARF and p16INK4a. Results suggest that DNMT3B over-expression may be involved in the suppression or lower expression of p14ARF and p16INK4a observed in esophageal squamous cell carcinoma.
- Results uncover an unexpected role for the p16(INK4a)-Rb pathway and provide a new insight into how senescent cell-cycle arrest is enforced.
- expression of p14(ARF) does not significantly alter ribosome biogenesis but inhibits polysome formation and protein translation
- expression significantly correlated with biological behavior of oral squamous cell carcinoma
- p16 expression was seen in 40% of esophageal dysplasia, 27% of esophageal squamous cell carcinoma and 100% of normal mucosa.
- the CDKN2A A148T variant seems to contribute to early-onset breast cancer in Poland
- Linkage of flat mole count to the CDKN2A gene region (9p21)was replicated with in 424 families with 1024 twins and siblings, plus genotypes for 690 parents.
- Overexpression of p16 and CDK4 in the cytoplasm, as well as loss expression of p16 in the nucleus might be important in the evolution of colorectal carcinoma from adenoma and, of adenoma from normal epithelia.
- Methylation of the p16 is associated with advanced esophageal squamous cell carcinoma
- Promoter methylation of cyclin-Dependent Kinase Inhibitor p16 is associated with malignant fibrous histiocytomas
- Using pancreatic juice to detect mutations of p16 can help distinguish patients with pancreatic cancer from those without evidence of pancreatic neoplasia.
- Overexpression of p14ARF and pl6INK4A was associated with follicular adenomas, follicular carcinomas and papillary carcinomas of thyroid
- The p16 gene promoter was hypermethylated in pterygia, and this hypermethylation was strongly linked to expression of the positive expression of DNMT3b protein and to the suppression of p16 protein.
- The M53I mutation in CDKN2A is a founder mutation that predominates in melanoma patients with Scottish ancestry
- p16 gene alterations are associated with papillary thyroid carcinoma
- Smoking was not associated with p16 or ppENK hypermethylation in pancreatic cancer patients
- There are different immunohistochemical expression patterns of p16INK4A and p53 between intraductal papillary-mucinous neoplasm and pancratic intraepithelial neoplasm
- By comparing the expression of p53, cyclin D1, p16, hTERT, and TSP-1 in spontaneously regressing keratoacanthoma and squamous cell carcinoma, the changes in the expression of these proteins to specific stages of skin carcinogenesis, is defined.
- deletion in the INK4a/ARF locus might contribute to tumor progression in renal cell carcinoma at least partly by functional inactivation of wild-type p53
- Only p16 (INK4A )and TIMP3 were methylated consistently in medulloblastomas (p16 (INK4A ) 14%, TIMP3 11%) and p16 (INK4A) also in anaplastic ependymomas (1/4 tumors).
- aberrant hypermethylation of the key cell cycle regulatory genes occurs at a relatively high frequency in pituitary adenomas, especially in RB1 pathway genes with promoter hypermethylation of the p16(INK4a) gene being the most common deregulation
- Our results show that mutations of CDKN2A occur infrequently in these high-risk groups, and that they occur mainly in exons 1alpha and 2.
- many human cell types undergo senescence by activation of the p16(INK4a)/Rb pathway, and that introduction of Bmi-1 can inhibit p16(INK4a) expression and extend the life span of human epithelial cells
- Reduced or absent expression showed no significant correlation with the clinicopathological parameters of rhabdomyosarcoma, except for the age at diagnosis.
- founder mutation (ins113Arg) in one family and a large duplication encompassing the CDKN2A gene locus in another family; moreover, a debated polymorphism (Ala148Thr) was found in nine families
- Decrease of expression of p16INK4 was significantly correlated with methylation.
- the N-terminal region of the p14(ARF) protein is involved in binding to c-Myc and N-Myc proteins
- Inactivation of p16 is associated with malignant transformation, contributing to a differentiation defect
- p16(INK4a) ELISA has a similar sensitivity and slightly better specificity for CIN3
- This study demonstrates that ARF plays a direct role in regulation of Rb and suggests that inactivation of ARF may lead to defects in both p53 and Rb pathways in human cancer development.
- Data suggest that the region spanning -62 to +1 bp of p16(INK4a) promoter plays a role in p16(INK4a) transcription regulation.
- The stabilization effect exerted by TBP-1 requires an intact N-terminal 39 amino acids in ARF and occurs independently from N-terminal ubiquitination of the protein.
- It might be possible that HPV infection and mutations in the exon 2 of CDK4 play a causal role in malignant transformation in a small number of squamous carcinomas of the head and neck region.
- Study shows that the ability of the oncogene BMI1 to repress the INK4A-ARF locus requires its direct association and is dependent on the continued presence of the EZH2-containing Polycomb-Repressive Complex 2 complex.
- CDKN2a polymorphism 500 C/G correlated with Ala148Thr but) no correlation was observed between the 500 C/G polymorphism and age, localization of the primary melanoma and survival time.
- Observation that silencing of p16 expression augments DNA damage-induced apoptosis in cervical cancer cells offers alternative strategies for anti-cancer therapies for human cervical cancer.
- Effects of exogenous p16(ink4a) gene on biological behavior of human lung cancer cells are reported.
- CDK4 and CDK6n delay senescence by kinase-dependent and p16INK4a-independent mechanisms.
- Telomere dysfunction and inactivation of the p16(INK4a) pathway might play a role for pyrothorax-associated lymphoma
- Results show that p16 is consistently expressed in tubal metaplasia, less and only patchy expressed in the normal Fallopian tube, and is paralleled by aberrant expression of cell cycle proteins.
- p14ARF signals through hAda3 to stimulate p53 acetylation and the induction of cell senescence
- These findings provide the first direct evidence that the p16(INK4a)/ARF/p15(INK4b) genetic region and the senescence machinery are active in physical ageing in heterogeneous human populations.
- We could detect colorectal cancer related genetic alterations by analyzing stool DNA with a sensitivity of 64% and 20% and a specificity of 95% and 100% for Long DNA and p16 respectively.
- Polymorphism of p16 was not associated with the risk of epithelial ovarian cancer development and progression.
- (i) an increase in p16(ink4a) expression in normal lymphocytes is linked, in part, to the number of cell doublings before the occurrence of replicative senescence and (ii) this process is maintained in leukemic cell populations of numerous patients.
- Homozygous deletion and hypermethylation of p16 gene may play an important role in the initiation and development of manifestations seen in endemic arseniasis including carcinogenesis.
- p16gamma, like p16(INK4A), induced cell-cycle arrest at G(0)/G(1), and inhibited cell growth in colony formation assay.
- p16gamma: a novel transcriptional variant of p16INK4A
- The evaluation of a large number of actinic keratoses specimens have found a low gene mutation rate in low-graded AK lesions. p53 mutations rather than p16(INK4a) and/or Ha-ras mutations may be an early event in the development of AK to cutaneous SCC.
- a carrier of the founder CDKN2A [p.Leu113Leu;p.Pro114Ser] mutation as well as two MC1R moderate-risk variants, [p.Arg151Cys(+)p.Arg163Gln] developed 22 primary melanomas in the 3 years that followed initiation of levodopa therapy for Parkinson's disease
- p14(ARF) hypermethylation and MGMT hypermethylation constitute distinct molecular pathways of astrocytoma progression, which could differ in biological behavior and clinical outcome.
- p16 may be implicated in the development of high-grade serous neoplasia within the ovary and elsewhere within the female genital tract.
- alteration of p16 could play an etiologic role, without any association to HPV infections, in rare endometrial carcinomas
- results show that germline mutations at the CDKN2A locus are rare in sporadic melanoma in Latvia
- expression of P16(INK4A) in developing TAL1xLMO1 thymocytes blocks leukemogenesis in the majority of the mice
- p16 is a more sensitive and specific marker for identifying high-grade squamous intraepitelial lesions (HSIL-s).
- Promoter hypermethylation of p16 was observed.
- Loss (homozygous deletion or single copy) of CDKN2A was not prognostically significant in Ewing's sarcoma.
- p16INK4a modulates glycomic profile and galectin-1 expression to increase susceptibility to carbohydrate-dependent induction of anoikis in pancreatic carcinoma cells
- findings suggest that hepatitis B virus X protein may play an important role in the early stage of HBV-associated hepatocarcinogenesis via induction of hypermethylation of p16(INK4A) promoter
- p16 is a highly sensitive marker for cervical epithelial dysplasia.
- elevated level of histone methylation resulted in the downregulation of the p16(Ink4a) gene
- Abrogation of the p16 is associated with head and neck squamous cell carcinomas
- p16INK4A to be a key factor in the regulation of human mesenchymal stem cells growth and is associated with cellular senescence.
- study of EGFR, HER2, TP53& KRAS mutations of p14arf expression of non-small cell lung cancers in relation to smoking
- The overexpression of p16 in uterine serous carcinoma is unrelated to HPV.
- immunohistochemical overexpression of p16 is linked to the presence and pathologic grade of human papillomavirus-induced precancerous cervical lesions.
- BMI-1 mediated repression of p16(ink4a) may contribute to an increased aggressive behavior of stem cell-like melanoma cells.
- Epstein-Barr virus-encoded latent membrane protein 1inhibited p16(INK4A) expression, promoted phosphorylation of p105 Rb and upregulated E2F1 expression and overexpression of E2F1 alone was sufficient to upregulate telomerase activity.
- a significant proportion of pancreatic ductal adenocarcinomas is characterized by simultaneous protein alterations regarding p16 & cyclin D1 genes; this mechanism of genetic deregulation in cell cycle potentially explains in part the aggressive phenotype
- Low expression of p16 was detected but had no effect on survival or recurrence in the univariate analysis.
- the melanoma-predisposing proline-48-threonine mutation of p16 in Hungarians may show a common founder either in Italy or in Hungary
- Results show that p14ARF regulates E2F-1 ubiquitination and degradation via a p53-dependent mechanism.
- PAX3-FKHR fusion gene of rhabdomyosarcoma cooperates with loss of p16INK4A to promote bypass of cellular senescence
- Elevated expression of cell-cycle regulators p16(INK4A), p21(CIP1), and cytoplasmic/nuclear beta-catenin correlated with increased colorectal cancers risk, as did elevated expression of survivin and human telomerase reverse transcriptase.
- correlation between p16 gene deletion and mammary gland carcinoma
- significant difference was detected between esophageal cancer and non-tumorous tissue in p16 expression; a significant correlation was observed among p53, COX-2 and p16 expression
- Aberrant methylation of multiple genes (E-cadherin, estrogen receptor, RB1 , p16, p15, p14, and MGMT) is involved in gastric carcinogenesis.
- This review focuses on the extensive studies that uncover the involvement of INK4 proteins in senescence, apoptosis, DNA repair, and multistep oncogenesis.
- ISOC2 is a novel functional protein, which is able to bind and co-localize with a tumor suppressor gene p16(INK4a).
- combined with screening of K-ras mutations and allelic losses of tumor suppressors p16 and DPC4 represents a very sensitive approach in screening for pancreatic malignancy.
- In patients with ulcerative colitis, hypermethylation of p14 ( ARF ) seems to be associated with an early stage of dysplasia.
- Expression of p16INK4 and also cyclin B1 correlate significantly with long-term survival in renal cell carcinoma.
- Expression may be reduced in some early gastric carcinomas.
- The detection of the homozygous deletion of the p16 gene in pleural effusion may be a useful adjunct to the cytological and histological examinations of pleural effusion.
- TWIST plays a key role in the continuous proliferation of immortalized cells. Over-expression of TWIST results in down-regulation of p14(ARF), which leads to the impairment of DNA damage checkpoint in response to genotoxic stress.
- germline mutations of CDKN2A at risk for melanoma occur in the Brazilian population, and that these mutations likely originated in Europe
- the tumor suppressor activity of ARF in melanoma-genesis is p53 independent [news]
- Results allow the dissection of the "protein-protein binding" and "CDK4 inhibition" functions of P16, show that the difference between tumor suppressing and oncogenic functions of P16 and gankyrin, respectively, mainly resides in a single residue.
- We did not find p16, p14, and p57 to be useful as prognostic markers in stage III ovarian cancer
- Did not find high mutation rates of CDKN2A in multiple primary and familial malignant melanoma in German patients.
- ARF pathway is required for the elimination of cells with aberrant CD43 expression.
- There is more frequent p16 hypermethylation in mantle cell lymphoma and p15 or Rb1 hypermethylation in follicular lymphoma.
- Authors describe the characterization of a novel strain of human diploid fibroblasts (designated Milan HDFs) from an individual who is homozygous for the R24P mutation in p16INK4a.
- results suggest that mutation of p16/CDKN2 gene was a common factor in development of malignant mucosal melanomas & adenoid cystic carcinomas
- Expression of p16 was significantly correlated with unfavorable prognosis in gastrointestinal stromal tumors.
- The methylationn frequency in malignant pleural mesothelioma was 11.4%. Methylation did not correlate to outcome but to improved survival in unmethylated malignant pleural mesothelioma with extrapleural pneumonectomy.
- smoking can influence the methylation level of the promoter region of p16(INK4a), and that this occurs in tumor tissues more frequently than in normal tissues
- In summary, p16 methylation is very frequent among non-small cell lung carcinoma patients, and correlates with heavy cigarette consumption only in disease-free smokers.
- p16 in the development of PA and in the progression of pleomorphic adenoma (PA) and carcinoma ex pleomorphic adenoma (CXPA) of the parotid gland.
- Loss of heterozygosity (LOH) of the hDMP1 gene was detectable in approximately 35% of human lung carcinomas, which was found in mutually exclusive fashion with LOH of INK4a/ARF or that of P53. DMP1 is a pivotal tumor suppressor for human lung cancers.
- Results identified CDKN2A EX2 loci showing significant differential DNA methylation levels between tumor and non-tumor lung and highly significant hypermethylation in adenocarcinoma.
- nucleolar localization determines the stability of ARF but not its primary function
- Results suggest that methylation is the predominant mechanism of inactivation of the CDKN2A in ESCC.
- in colorectal carcinoma patients, the p16 methylation score significantly increased with tumor stage; the p16 methylation score was significantly higher in patients with lymph node metastasis and tumor invasion to the veins
- There is a high level of association between the absence of p16 protein expression levels, CDKN2A gene promoter hypermethylation, and chromosome 9 aneuploidy.
- Premature senescence of balding dermal pipilla cells in vitro in association with expression of p16(INK4a)/pRB suggests that balding cells are sensitive to environmental stress
- The results show that the LOH pattern in genes p16 and p14ARF occur as well in leuplakia with malignant transformation as in leukoplakia, that do not show clinical alterations. The rate of allelic loss did not differ significantly.
- data show that the CDKN2A p.G23S mutation is an important cause of hereditary melanoma in Tuscany
- ERK activation with some other pathway(s), activated through the HGF receptor, are required to up-regulate p16 and p21 expression, that of p21 contributes to suppression of Cdk2 activity leading to inhibition of proliferation of HGF-treated HepG2 cells.
- ARF is a serine phosphorylation-dependent coregulator of topoisomerase I in vivo, and it regulates cellular sensitivity to camptothecin by interacting with topoisomerase I.
- INK4a/ARF promoter hypermethylation may serve as a marker of global methylation dysregulation.
- Protein expression neither of p16(INK4a) nor of p53 correlated with high-risk human papillomavirus status
- Variants are associated with multiple primary cutaneous melanomas in a Norwegian population.
- The CDKIs p16 and p27 are associated with tumour progression in melanoma, but do not reliably predict recurrence or survival.
- mutant p53 loses its ability to suppress DNMT1 expression, and thus enhances methylation levels of the p16 ( ink4A ) promoter and subsequently down-regulates p16(ink4A )protein.
- expression leading to endothelial cell proliferation is suppressed by Rem2
- Senescent NHP cells that have lost progenitor markers and accumulated p16INK4a (p16) protein expression, appear to be the preferential fusion targets. Tumorigenicity of the NHP/293T-L hybrid cells was inhibited by exogenous p16 as well as hTERT.
- loss of expression of CDKN2A via deletion plays an important role in the pathogenesis of human NMSC. Deletions in CDKN2A could arise spontaneously, perhaps during tumour progression.
- Inactivation of CDKN2A and B genes constitute an important step in chordoma development.
- Homozygous deletion, a combination of LOH and promoter hypermethylation, and multiple LOH are major mechanisms of p16 inactivation in gallbladder cancer.
- p16 can serve as a reliable immunohistochemical marker in distinguishing uterine leiomyosarcomas from leiomyomas and its benign variants
- CDKN2A FISH analysis can give false negative results in cases with small microdeletions
- Poorly differentiated colorectal adenocarcinomas strongly correlates with miscrosatellite instability and methylation of the p16 and hMLH1 promoter region.
- p16 is preferentially expressed in eiomyosarcoma with only rare leiomyoma showing positivity
- Nordihydroguaiaretic acid reverses p16INK4a CpG island hypermethylation, and restores its transcription and expression in human breast and colorectal cell lines.
- Examined association between MTHFR/thymidylate synthase gene polymorphisms and methylation of p16(INK4A) and hMLH1 genes in spontaneously aborted embryos with normal chromosomal integrity.
- Identification of a novel germline variant, G89D, that was strongly associated with increased melanoma risk and appeared to be an Icelandic founder mutation.
- Immunofluorescence technology to quantify cervical cell expression of two biomarkers p16(INK4A) and Mcm5 was developed and evaluated by both microscopy and flow cytometry.
- We immunohistochemically analyzed the expression of p21, p27, p14, p16, p53 and proliferation marker Ki67, in 67 low and high grade astrocytic tumors
- An important role for autophagy in tumor suppression via full-length ARF in both p53-dependent and p53-independent manners, depending on cellular context.
- High p53 expression level with low MDM2 and p14 ARF levels may be the characteristic features of low differentiated endometrial carcinoma.
- a high level of expression of MIB-1 indicates a low grade of tumor, whereas high expression of p16INK4a indicates a highly differentiated cervical adenocarcinoma
- p14ARF silencing may be an important mechanism in MCC tumorigenesis, and thus a potential target for therapeutic intervention in this highly aggressive tumor type.
- p16INK4a immunohistochemistry as an adjunct to conventional H&E-stained specimens contributes to a more reproducible diagnosis of cervical intraepithelial neoplasia and may be a valuable aid for the interpretation of cervical histology.
- study identified aberrant p16INK4 expression in different stages of urothelial lesions; urothelial carcinoma in situ showed overexpression of p16INK4, suggesting a role of INK4a mutation as an early event of bladder carcinogenesis
- Alterations of SH3GL2 and CDKN2A loci have a synergistic role in the development of early-onset breast cancer.
- Despite the fact that p16 is important in non-small cell lung cancer carcinogenesis, the data obtained do not allow the prognostic impact of this biological marker to be established.
- Results indicate that TBX3 represses expression of p14(ARF) tumor suppressor in breast cancer.
- p14ARF mRNA expression was suppressed in 13 of 37 cases of ATLL, among which 9 cases showed inactivation of both p14ARF and p16INK4a, and 4 cases showed inactivation of p14ARF alone. inactivation of p14ARF and mutation of p53 are mutually exclusive.
- specific modes of inactivation of p16 in Head and neck squamous cell carcinoma are related to specific patient risk profiles
- Alterations in p14ARF gene by deletion and/or methylation were observed in 30% of the oral carcinoma cases. p14ARF methylation is associated with a lower recurrence rate. Promoter methylation of p16INK4A was associated with increased disease recurrence.
- Lowered p16 expression represented an unfavourable prognostic index in ovarian cancer.
- High frequency of hypermethylation of p16 was detected in the precancerous lesions; no hypermethylation was found in normal epithelium. Hypermethylation may be involved in the pathogenesis of oral precancerous lesions associated with betel-quid chewing.
- The morphology and cell cycle proteins immunoexpression of the novel probable preinvasive lesion - bronchiolar columnar cell dysplasia (BCCD), is decribed.
- deletion in CDKN2 gene in melanoma patients is described
- uncommon coexistence of a germline mutation in two suppressor genes, RET and CDKN2A in multiple endocrine neoplasia 2a
- Expression of p16 increased with uterine cervical lesion progression
- Immunohistochemical tests for p16 (INK4A) and cyclin E could help in early diagnosis of cervical carcinoma.
- the ability to promote Lys(63)-mediated polyubiquitination of COMMD1 is a novel property of ARF independent of p53
- Analysis of the pattern of expression of these biomolecules showed increased p16-positive phenotypes and decreased cyclin D1- and pRB-positive phenotype among the invasive tumors compared to low-grade CIN lesions
- Inactivation of p16 gene in histologically normal bronchi could aid the identification of individuals at risk of developing squamous cell carcinoma of the lung.
- c-Jun translocates B23 and ARF from the nucleolus after JNK activation by means of protein interactions
- deletion of the locus harborning the p16 gene may be helpful for differentiating between malignant mesotheliomas and reactive mesothelial proliferations.
- p14(ARF) methylation was present in 61 of 188 colorectal cancers. 4 major haplotypes were identified within a block (-4256 T-->C, -3631 T-->C, -1477 G-->A, +20,188 T-->C). p14(ARF) promoter methylation was associated with CCAT and CTAC haplotype.
- Deletion rate was 25/54 (46%), of these 19/25 (76%) were homozygous. Small deletions (<200 kb) were found in 8/25 (32%) and the smallest deletion was <30 kb.
- investigation of the involvement of the CDKN2A, CDKN2B and p53 genes in actinic keratosis (AK) and in the progression of AK to squamous cell carcinoma
- balance between Polycomb group (PcG) silencing and SWI/SNF activation affects epigenetic control of the INK4b-ARF-INK4a locus in malignant rhabdoid tumors
- Large-scale analysis of cell cycle regulators in urothelial bladder cancer identifies p16 and p27 as potentially useful prognostic markers
- p16 appears not to be directly involved in the development of sinonasal or urothelial inverted papilloma.
- p16(INK4a), p21(WAF1/CIP1), p27(KIP1), and p53 are expressed in human corneal endothelial cells despite donor ages.
- Methylation of the promoter region of the p16 gene in patients with stage I NSCLC treated with curative intent by means of surgery is associated with early recurrence.
- There is an increased melanocytic nevi and nevus density in a G-34T CDKN2A/p16 melanoma-prone pedigree.
- Incresed expression of p16(INK4a) and telomeres shortening were observed with age in some stem and progenitor cells.
- Oncolytic herpes virus with defective ICP6 specifically replicates in quiescent cells with homozygous genetic mutations in p16.
- The expression of p16(INK4A) protein is significantly higher in endocervical adenocarcinoma than in endometrial adenocarcinoma
- p53 and p16(INK4A) are promising candidates for the pulmonary molecular screening of heavy smokers healthy individuals.
- CDKN2A was found to be methylated significantly more frequently in NSCLC tissues than in non-cancerous tissues.
- Review of molecular mechanisms underlying the functional loss of cyclindependent kinase inhibitors p16 and p27 in hepatocellular carcinoma.
- p16INK4a hypermethylation is associated with hepatocellular carcinoma
- p16 expression is suppressed by miR-24 in human diploid fibroblasts and cervical carcinoma cells
- Association study of common variation spanning the CDKN2A/CDKN2B locus confirms the strong association between the distal susceptibility variant and type 2 diabetes in the French population.
- CDKN2A overexpression was associated with decreased event-free survival in meningiomas.
- activation of hTERT alone appears to be insufficient for immortalization of prostate epithelial cells because methylation of p16(INK4a) promoter has been found to be involved in the immortalization process
- These findings uncover a feedback regulatory circuit in the astrocytic lineage and demonstrate tumor suppressor role for p18(INK4C) in human glioblastoma wherein it functions cooperatively with other INK4 family.
- Three samples with mutations identified at the local centres were not detected by DHPLC. The low rate of CDKN2A mutation detection is not due to failure to detect mutations and implies the existence of other high penetrance melanoma susceptibility genes.
- p16 promoter hypermethylation is an important event in gastric carcinogenesis
- P16 inactivation by homozygous deletions or methylation is a frequent event in Japanese patients with malignant pleural mesothelioma
- Founder deletion (p16-Leiden) in Dutch melanoma families does not account for the atypical nevus phenotype that segregates in both p16-Leiden carriers and non-carriers and is a risk factor and a precursor lesion for melanoma.
- Aberrant BRAF and INK4A functionally interact to promote growth and survival of melanoma cells.
- Genistein induces the expression of tumor suppressor genes p21 (WAF1/CIP1/KIP1) and p16 (INK4a) with a concomitant decrease in cyclins in prostate cancer cells.
- frequent and variable p14 gene abnormalities in glioma cell lines
- p14(ARF) inhibits Tat transactivation of HIV-1 LTR by promoting Tat degradation via an ubiquitin-independent pathway.
- P16 hypermethylation in mucosa of colorectal cancer patients was identified as an independent prognostic parameter for cancer-specific survival.
- Report high-risk human papillomavirus infection and p16INK4a protein expression in benign/malignant laryngeal lesions.
- Of the molecular modifications described for renal carcinoma, aberrations in the p16 gene are frequent
- in bronchial squamous cell carcinoma, p14arf (cyclin-dependent kinase inhibitor 2A) expression loss or its nucleolar relocalisation both increased at severe dysplasia;nucleolar relocalisation of p14arf was associated with that of Nucleoplasmin
- Loss of p16/Rb protein (pRb) expression and overexpression of cyclin D1/CDK4 were observed in 49%/40% and 37%/37% of gastric carcinomas, respectively.
- Nuclear p16 expression is absent in normal gallbladder epithelium and is a frequent event in high-grade dysplasia of the gallbladder and gallbladder adenocarcinoma.
- Hypertension induces cellular senescence via p16(INK4a), possibly through p38, thereby contributing to hypertensive target organ damage.
- Genetic and epigenetic analyses of the human 9p21 locus indicate that modifications of ARF occur independently of p16 inactivation in human melanoma and suggest that ARF is more frequently inactivated than p16.
- The p16INK4A promoter was heavily methylated in a subset of paragangliomas and showed moderate suppression in malignant cases
- Mel-18 overexpression showed reduced glycogen synthase kinase-3beta phosphorylation, beta-catenin nuclear localization, T-cell factor/lymphoid enhancer factor promoter activity, and cyclin D1 mRNA level
- Mitochondrial p32/C1QBP is a critical mediator of p14ARF-induced apoptosis.
- PPARgamma promotes cellular senescence by inducing p16(INK4alpha) expression
- P16 protein has a prognostic value in assessment of disease free survival
- Data found homozygous deletions in exon 3 of the p16INK4a gene in two schwannomas.
- aberrant methylation of p16 and EDNRB was highly prevalent in leukemia patients in Taiwan.
- YY1, HDAC3 and HDAC4 restrained cell senescence by repressing p16(INK4a) expression through an epigenetic modification of histones
- CDKN2A/p16+ test reporting enhances compliance with early detection measures for melanoma families.
- No significant associations were observed between p16 homozygous deletions and gender, age, smoking history, stage, and prognosis.
- this is the first report that experimentally links the tumour suppressor p16 to the process of lymphangiogenesis.
- NIAM is a nuclear interactor of ARF and Mdm2
- p16(INK4a) distribution did not correlate with smokeless tobacco keratosis (STK) grade and does not appear to be related to the detection of HPV DNA by PCR in either STK or in squamous cell carcinoma.
- Contribution of large rearrangements in CDKN2A to the disease in melanoma-prone families was examined using multiplex ligation-dependent probe amplification.
- p16-Leiden gene is associated with increased risk of melanoma and pancreatic cancer.
- A lesser proportion of the p16 deletion in T-ALL patients was observed.
- Andrographolide inhibits human colorectal cancer Lovo cell growth by G1-S phase arrest and inducing the expression of p53, p21 and p16.
- CDKN2A can be implicated in the carcinogenesis process of only a subset of gastric neoplasias.
- Results indicate that in Chinese Hans, common variants in CDKN2A loci independently or additively contribute to type 2 diabetes risk, likely mediated through beta-cell dysfunction.
- p14(ARF) mRNA expression was notably increased in retinoblastoma but p14(ARF) protein was undetectable.
- senescence of primary NHP cells expressing progenitor cell markers CD44, alpha2beta1, p63, hTERT, and CK5/CK18, involves loss of telomerase expression, up-regulation of p16, and activation of p53.
- the gene CDKN2A, is subject to homozygous and heterozygous deletions in neuroblastoma tumors
- Aberrant expression may reflect early genetic events during the progression of Barrett esophagus-associated carcinogenesis.
- Stresses and stimuli that reduce CtBP-mediated repression are associated with increased p16 expression; therefore, CtBP may provide a common final target for regulating the balance among tumor suppression, regenerative capacity, and senescence
- There is a role for caveolin-1 in degenerative rather than age-induced changes in the nucleus pulposus. A positive correlation was identified between gene expression of caveolin-1 and p16INK4a (biomarker of cellular senescence).
- p14(ARF) hypermethylation was detected in 16 (53.3%) of hepatocellular carcinoma
- Study show that polymorphisms in CDKN2A were associated with type 2 diabetes risk in the studied population.
- Results show that p14ARF associates with Brca1, which may play a major role in tumor suppression.
- Promoter methylation of p16 is a promising biomarker for malignant transformation of OED.
- A paucity of mutations in CDKN2A/ARF suggesting that in the Polish population this gene does not contribute significantly to early-onset breast cancer, pancreatic cancer and malignant melanoma.
- The nucleolar p19(ARF) is incapable of inducing autophagy from within the nucleolus.
- analysis of the coordinated immediate responses by p16INK4A and p53 pathways in UVB-irradiated human skin cells
- An association between p16INK4 and CIN2 and CIN3 lesions was found which may indicate that p16INK4 may be a strong marker for "neoplastic lesions" induced by HPV and not just an infection marker.
- Promoter hypermethylation of the p16 gene is associated with poor prognosis in recurrenct early-stage hepatocellular carcinoma.
- p16 plays an important role in cancer pathogenesis
- study concludes that p16 gene is involved in the pathogenesis of skin basal cell carcinoma in view of increased p16 mRNA and expressed protein within tumor cells
- Study concludes that CDKN2A is a promising new candidate gene potentially contributing to AD susceptibility on chromosome 9p.
- the analysis of p21cip1, p27kip1, and p16INk4a by immunohistochemistry could be useful in the management of patients with papillary thyroid carcinoma
- p16 ink4a and L1 immunohistochemistry can be helpful for estimating the biologic potentiality of low-grade squamous cervical lesions
- 27/30 (90%) of Atypical lipomatous tumor (ALT)/well-differentiated liposarcoma (WDLPS) showed positive staining of either p16, MDM2, or both, whereas no staining was observed in all the deep-seated lipomas
- Underexpression of p16 is associated with lymph node metastases in laryngeal squamous cell carcinoma.
- p16 alterations and particularly p16 gene deletions in endometrial carcinoma are associated with increased incidence of metastases.
- positive expression rate and co-expression rate of P21WAF1/CIP1 and P16 proteins could reflect the malignant grade of glioma to some extent, and they can be considered as a sensitive index for glioma grading
- The p16INK4a/cyclin D1/pRB pathway was altered in gastrointestinal tract endocrine tumors
- In this immunohistochemical study, 80% of all vulvar intra-epithelial neoplasia were positive of p16(INK4A).
- The present study has shown a high prevalence of CDKN2A mutations affecting p16INK4A in Slovenian population of familial melanoma patients
- Cooperative effect of p21Cip1/WAF-1 and 14-3-3sigma on cell cycle arrest and apoptosis induction by p14ARF
- Correlation of p16/INK4a gene damages and protein expression in the tumor tissue of sporadic breast cancer
- in addition to high-risk classification, p16 expression might be an indicator for "very high risk gastrointestinal stromal tumors."
- germline epimutation of the CDKN2A gene is not found in familial melanoma
- p16 methylation was significantly associated with H. pylori infection in precancerous gastric lesions, suggesting that H. pylori infection could potently induce methylation of p16 CpG island
- These results indicate that MGMT and/or p16 aberrant methylation may play an important role in colorectal cancer.
- CDKN2A deletion is a significant secondary abnormality in childhood acute lymphoblastic leukemia strongly correlated with phenotype and genotype
- Can initiate a cyclin-dependent kinase (CDK)4- or CDK6-dependent autonomous senescence program that is disabled by inherited melanoma-associated mutations.
- Results indicate that both p16(INK4a) and p21(WAF1/CIP1) are required for the opioid growth factor (OGF)-OGF receptor axis to inhibit cell proliferation in normal cells.
- These findings implicate MBD2 in transcriptional repression of the methylated p14(ARF) tumor suppressor gene and suggest that repression by MBD2 selectively affects a subset of methylated promoters.
- Evaluation of p16 and ESR1 promoter methylation in blood using real-time PCR appears to be very useful for lung cancer diagnosis
- beta-catenin/TCF4 regulates cell cycle promoting (c-MYC, CYCLIN D(1)) and inhibiting genes (p16(INK4A)) at the same time in the mesenchymally differentiated tumor cells at the front of invasion.
- inducible expression of p16(INK4a) sensitized a melanoma cell line to death induced by melphalan or actinomycin-D; study shows high expression of p16(INK4a) or the absence of activated B-RAF correlates with in vivo response of melanoma to cytotoxic drugs
- Lack of p16/CDKN2A deletion significantly predicted the survival of malignant mesothelioma patients.
- study shows clear evidence of increased risk of cancers other than melanoma in CDKN2A families carrying the p16-Leiden mutation
- high frequency of CDKN2A mutations are associated with multiple primary melanoma.
- CDKN2A deletion is associated with acute lymphoblastic leukaemia.
- p16INK4a and p14ARF aberrations are common in oral verrucous leukoplakia. Loss of heterozygosity occured in 45% of PVL patients.
- Single nucleotide polymorphism in CDKN2A is associated with type 2 diabetes.
- Methylation of the p16 gene was detected more frequently in nontumorous liver than in normal liver using the TaqMan PCR method. Methylation indices also were significantly higher in nontumorous than in normal liver.
- determined the p16 mutation spectrum for a cohort of 304 patients with Barrett's esophagus; results suggest the environment of the esophagus in BE patients can both generate and select for clones with p16 mutations
- Immunostaining with p16 should be considered as a highly desirable addition to the histologic evaluation of cervical biopsy specimens in high-risk human papillomavirus positive women.
- Alterations in both the p53 and p16-Rb pathways are associated with squamous cell carcinoma arising in mature cystic teratoma.
- deregulation of the p16(INK4a) senescence pathway is involved in the development of myoepithelial tumours
- found homozygous deletion of p16/CDKN2A in 6 out of 7 cases of anaplastic astrocytomas and 20 out of 33 cases of glioblastoma multiforme, in total 26 out of 40 cases of malignant gliomas
- P16(INK4A) was overexpressed in 71.7% of Hodgkin lymphoma, was in the nucleus and cytoplasm of HRS cells, and was inversely related to EBV-LMP1
- Data show that 87.9% of the patients with invasive lesion showed overexpression of p16(INK4a), in comparison with 37.6% of those with in situ lesion, demonstrating overexpression of p16(INK4a) as a risk of invasion of the basal layer by dysplastic cells.
- p16 genes and their 9p21 locus have various roles in the pathogenesis of oral squamous cell carcinoma
- reduced expression of pl6 is a common event in pheochromocytomas, and the primary cause for such downregulation is inactivating genetic abnormalities in the p16 gene
- overlapping E2F1/Sp1 site, being present in multiple copies in the p14ARF promoter, may serve as the targets for both E2F1 and Sp1, thereby playing a crucial role in response to some oncogenic signals and stimulators
- Using a panel of four genes (AHRR, p16INK4a, MT1G, and CLDN3) resulted in sensitivity and specificity of 50% and 68%, respectively and may have utility for early detection of esophageal squamous dysplasia and early ESCC.
- K-RAS point mutations, and anomalies of p16-RB1-cyclin D pathway could occur before LOH on 10q23 (PTEN) and microsatellite instability during tumor progression.
- of promoter hypermethylation of TIMP3, CDH1, DAPK, RASSF1A, p16INK4A and MGMT, only the epigenetic silencing of TIMP3 and CDH1 predicted a better outcome in head and neck squamous cell carcinoma
- DDB1-CUL4 and MLL1 complexes constitute a novel pathway that mediates p16 activation during oncogenic checkpoint response.
- CDKN2A CDKN2B and ANRIL is the susceptibility locus for coronary heart disease (CHD) and periodontitis.