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Validated All-in-One™ qPCR Primer for MLH1(NM_000249.3) Search again
Product ID:
HQP011235
(click here to view gene annotation page)
Powered by BiozSpecies:
Human
Symbol:
Alias:
COCA2, FCC2, HNPCC, HNPCC2, LYNCH2, MLH-1, MMRCS1, hMLH1
Gene Description:
mutL homolog 1
Target Gene Accession:
NM_000249.3(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 was identified as a locus frequently mutated in hereditary nonpolyposis colon cancer (HNPCC). It is a human homolog of the E. coli DNA mismatch repair gene mutL, consistent with the characteristic alterations in microsatellite sequences (RER+ phenotype) found in HNPCC. Alternatively spliced transcript variants encoding different isoforms have been described, but their full-length natures have not been determined. [provided by RefSeq].
Gene References into function
- hereditary and somatic mutations in sporadic endometrial adenocarcinoma
- mutational analysis in HNPCC
- binds Bloom syndrome protein; nuclear localization
- Further characterization of the mutational spectrum of MLH1 gene in HNPCC families.
- Mutational analysis of promoters of mismatch repair genes hMSH2 and hMLH1 in hereditary nonpolyposis colorectal cancer and early onset colorectal cancer patients: identification of three novel germ-line mutations in promoter of the hMSH2 gene.
- PMS2-MLH1 protein interactions diminished by single nucleotide polymorphisms in HNPCC
- hMutSalpha forms an ATP-dependent complex with hMutLalpha and hMutLbeta on DNA
- Large deletions have been detected in MLH1 in hereditary nonpolyposis colorectal cancer (HNPCC).
- Tumor-specific promoter hypermethylation of hMLH1 may be an early event in carcinogenesis of the stomach
- Mutation analysis of MLH1 and MSH2 genes performed by denaturing high-performance liquid chromatography
- Contribution of human mlh1 and pms2 ATPase activities to DNA mismatch repair.
- methylation density of a specific region plays an important role in gene inactivation of hMLH1 in colonic and gastric cancer cell lines
- Mutations within the hMLH1 and hPMS2 subunits of the human MutLalpha mismatch repair factor affect its ATPase activity, but not its ability to interact with hMutSalpha
- The expression of hMLH1 and hPMS1 was significantly low in some large B-cell lymphomas and in mantle cell lymphomas of the blastoid type and may be related to the natural history of these neoplasms.
- Association of Crohn's disease and ulcerative colitis with haplotypes of the MLH1 gene
- Frequent LOH at hMLH1, a highly variable SNP in hMSH3, and negligible coding instability occur in ovarian cancer.
- upregulation by ascorbic acid
- Eight mutations and two polymorphisms detected in Brazilian families with suspected Hereditary Nonpolyposis Colorectal Cancer
- Age of onset and tumor microsatellite instability (MSI) not associated with MLH1 promoter methylation may point to women with a genetic susceptibility to malignancies
- Loss of mismatch repair protein (mainly, Mlh1) expression was detected in 21 of the 52 (40.4%) colorectal carcinomas
- The type 1 methylation pattern affects MLH1 mRNA expression such that the majority of cases of high-frequency microsatellite instability in sporadic colorectal cancer exhibit type 1 methylation.
- Cellular effects of CPT-11 on colon carcinoma cells: dependence on p53 and hMLH1 status.
- Hypermethylation of HPP1 is associated with hMLH1 hypermethylation in gastric adenocarcinomas.
- Different molecular mechanisms underlie MLH1 sequence deletions in patients with Hereditary Nonpolyposis Colorectal Neoplasms.
- Biallelic inactivation of the MLH1 gene is a common epigenetic event in colorectal carcinogenesis when the promoter region is fully methylated.
- mutation analysis of K-ras and beta-catenin genes related to O-6-methylguanine-DNA methyltransferase and this protein status in human gallbladder carcinoma
- genomic deletions in both MSH2 and MLH1 genes play a considerable role in the pathogenesis of HNPCC and should be part of the routine HNPCC mutation detection protocols.
- Mutations in the hMLH1 gene cause inactivation of the MMR gene in renal cell carcinoma.
- Mutations in hMLH1 cause inactivation of the MMR gene in renal cell carcinoma.
- Data show that hypermethylation of human MLH1 may play a role in the early stage of development of some gastric carcinomas.
- We report that expression of wild-type hMLH1 protein causes 19-fold increase in mutation rates, which was due to the ability of hMLH1 to interact with E coli MutL and MutS
- extensive methylation of hmlh1 is associated with the presence of a defective DNA mismatch repair pathway resulting in microsatellite instability in acute myeloid leukemia
- Microsatellite instability and hypermethylation of the promoter of this protein are involved in Richter's transformation of chronic lymphocytic leukemia.
- CpG methylation of MGMT and hMLH1 promoter in hepatocellular carcinoma associated with hepatitis viral infection.
- Promoter hypermethylation represents a major mechanism of the hMLH1 gene inactivation in head and neck squamous cell carcinoma.
- loss of hMLH1 expression in colorectal cancer patients strongly associated with increasing age
- loss of MLH1 and MSH2 expression seen in approximately equal frequency in small intestine neoplasms with microsatellite instability
- Novel germline mutation in MLH1, with a deletion resulting in a frameshift and a premature stop codon (codon 228) noted in one Uraguayan HNPCC family
- There is mutation and methylation of this gene in gastric carcinomas with microsatellite instability.
- Mutations of this protein show microsatellite instability in human prostatic cancer
- Data show that alterations in global DNA methylation may influence tumor progression but are not directly associated with the inactivation of the mismatch-repair proteins hMLH1 and hMSH2.
- This is the first report in which genetic defects leading to disruption of mismatch repair function in a human melanoma have been identified.
- The degree, rather than region-specific methylation of CpG islands is critical for decreased MLH1 expression & the microsatellite instability phenotype. Hypermethylation of mismatch repair genes is the initial step in endometrial carcinogenesis.
- Our findings indicate that reduced expression of the MMR proteins may have an important contribution in the development of a subset of TCCs and suggest a potential role for MMR expression as prognostic indicators.
- Immunohistochemistry revealed decreased hMLH1 protein expression in 27% (8/30) of esophageal squamous cell carcinomas, hMLH1 promoter hypermethylation was not observed.
- role in methylation-induced G(2)/M arrest
- N-terminus of MLH1 confers interaction of MutLalpha and MutLbeta with MutSalpha.
- the hMLH1 promoter contains multiple redundant enhancer elements capable of independent promoter activation and may explain the association of this region with methylation silencing of hMLH1.
- Although mutator pathway was implicated in younger-age-onset colorectal carcinogenesis, many tumors appeared to evolve from different genetic events other than hMSH2 and hMLH1 mutations frequently identified in nonpolyposis colorectal cancer
- Ductal pancreatic carcinomas express hMLH1 protein irrespective of their differentiation
- A mutation in the hMLH1 promoter co-segregates with the HPNCC phenotype. The -42C > T mutation is within a putative Myb binding site. The mutated Myb binding sequence is less effective in binding nuclear proteins than the wild-type promoter sequence.
- One MLH1 deletion (exons 3-6) has been found in Lynch syndrome patients.
- findings suggest a novel mechanism of MLH1 in the induction p53 and apoptosis by inhibiting RNA polymerase II-dependent transcription on damaged DNA templates
- mutator phenotype dominates over the gradual accumulation of DNA hypermethylation in determining the genotypic features that govern the phenotypic peculiarities of colon cancer of the mutator pathway
- Some atypical polypoid adenomyoma of the uterus exhibit MLH-1 promoter hypermethylation with focal lack of MLH-1 immunostaining.
- hMLH1 is one of the most commonly mutated MMR genes in endometrial carcinomas and colorectal carcinomas.
- colocalization of pathogenic missense mutations with exonic splicing enhancers sites strongly suggests that their pathogenic effects are splicing related
- Reduced expression of MLH1 during CDDP-based chemotherapy is associated with advanced thoracic squamous cell carcinoma of the esophagus
- Inactivation of hMLH1 of DNA mismatch repair genes has an important role to play in the mutagenesis of the tumor-suppressor genes in alveolar soft part sarcoma.
- Loss of hMLH1 and/or hMSH2 expression was found in nine of 15 microsatellite instability-high ovarian endometrioid carcinomas.
- Microsatellite instability may be a consequence of hMLH1 promoter hypermethylation in mycosis fungoides patients and may prevent transcription in a subset of patients.
- the most prominent mismatch repair inactivation mechanism in sporadic colorectal cancer patients is the hMLH1 promoter hypermethylation which may have a role in the carcinogenesis of sporadic colorectal cancer.
- hMLH1 and hMSH2 gene mutations are present in radial growth-phase cutaneous malignant melanoma cell lines
- 4/6 (66.67%) and 1/6 (16.67%) mutations of hMSH2 and hMLH1 were identified in typical HNPCC and atypical HNPCC, respectively.
- Promoter methylation and hMLH1 expression are significantly associated with the MSI-H phenotype in colorectal cancers. (REVIEW)
- findings suggest that defective DNA mismatch repair, due to inactivation of DNA mismatch repair protein hMLH1 and hMSH2 protein, does not play a significant role in the pathogenesis of intraductal papillary-mucinous neoplasms of the pancreas
- MLH1 has a role in squamous cell carcinoma of larynx development
- MSH3 abrogation may be a predictor of metastatic disease or even favor tumor cell spread in MLH1-deficient colorectal cancers.
- Mutations of the MLH1 is associated with double primary cancers of the colorectum and the endometrium
- founder mutation in hereditary non-polyposis colorectal cancer patients from northern Italy
- All hereditary nonpolyposis colorectal cancer patients displayed microsatellite instability, with the half losing hMLH1 expression.
- Germline epimutation of MLH1 is associated with multiple cancers
- MLH1 plays an important role in laryngeal squamous cell carcinoma development and progression
- Proteolysis of MLH1 by caspase-3 plays a functionally important role in the execution of DNA damage-induced apoptosis.
- The presence of mutations of MSH2 and MLH1 in melanoma brain metastases, which has not been found in primary melanomas, indicates the high genomic instability of melanoma brain metastases.
- hMLH1 gene mutations, especially those of the first nine exons, are common in Chinese hereditary nonpolyposis colorectal cancer.
- Low predictive value of hMLH1 microsatellite and immunohistochemical analysis in Taiwanese hereditary nonpolyposis colorectal cancer
- Data show that DNA damage induces the accumulation of hPMS1, hPMS2, and hMLH1 through ataxia-telangiectasia-mutated (ATM)-mediated protein stabilization.
- hMLH1 methylation in plasma DNA has a role in progression of ovarian cancer after chemotherapy
- 2 cases of exon skipping and 1 case of partial intron inclusion with activation of a cryptic intronic splice site were found in MLH1.
- Aberrant promoter methylation of DNA mismatch repair enzyme MLH1 is detectable in a small number of acute myeloid leukemia cases.
- hMLH1 gene mutations, especially of the first nine exons, have been found more common than hMSH2 gene mutations in Chinese patients.
- 9 new mutations (c.632_633insT, c.808_811delACTT, c.845C>G, c.1625A>C, c.1730+1delG, c.1907T>C, c.1918C>T, c.2104-2A>G and c.2170T>A)were found in Korean HNPCC families.
- In HPCC patients, 7 new mutations were found: c.1023delG (p.R341Xfs); c.1127_1128dupAT (p.K377Xfs); c.1310delC (p.P437Xfs); c.677+3A>C (r.589_677del); c.1990-2A>G; c.122A>G (p.D41G); & c.2155_2156insATGTGTTCCACA (p.I719delinsNVFHI).
- The caqrcinogenesis of hereditary form of colon cancer with mutations in hMLH1 and hMSH2 genes involved in DNA repair is reviewed.
- hMLH1 gene, which was considered to be a pathogenic mutation. According to the Human Mutation Database and International Collaborative Group on HNPCC (ICG-HNPCC) Database, this is the first report of this type of deletion mutation in the hMLH1 gene.
- Loss of MLH1 gene is associated with genetic instability in testicular germ cell tumor
- Identification of MLH1 missense codons that impair DNA mismatch repair function.
- at pachynema, when chromosomes are fully paired, we find significant heterogeneity in the localization of the MutL homologs, MLH1 and MLH3, among human oocyte populations
- Two novel MLH1 germ-line mutations in hereditary nonpolyposis colorectal cancer have been identified.
- The observed profiles of hMLH1 methylation and microsatellite instability in gastric cancer, colorectal cancer, and NSCLC were quite different from each other
- Large genomic deletions which mainly present to MSH2 account for 20% of general pathological sequence changes of MSH2 and MLH1 genes in Chinese HNPCC patients.
- hMLH1/hMSH2 protein expression is constitutively higher in certain cell types of certain tissues, including the majority of tissues that are at increased risk of cancer in hereditary non-polyposis colon cancer (HNPCC)
- MLH1 promoter gene hypermethylation is associated in patients diagnosed with metachronouscolorectal neoplasms.
- characterization of nuclear import
- BRAF mutations proved to be absent in tumors from hereditary nonpolyposis colorectal cancer syndrome (HNPCC) families with germline mutations in the MMR genes MLH1 and MSH2.
- Chinese hereditary nonpolyposis colorectal cancer showed relatively frequent germline mutation of mismatch repair (MMR) genes
- Epithelial cells of CIN lesions showed a significant increase in the expression of both hMLH1 and hMSH2 proteins compared to non-neoplastic squamous epithelium.
- Colorectal cancers not expressing hMLH1 or hMSH2 may have distinct features from those expressing these mismatch repair proteins. p53 expression appears to be implicated in a compensatory pathway with mismatch repair proteins.
- positive staining was found in 33.3% and 53.3% for hMLH1 and hMSH2, respectively, in dysplastic nevi, and in 54.5% and 69.1%, respectively, in cutaneous melanoma
- Defective DNA MMR is uncommon in long-term survivors of pancreatic cancer and does not account for the survival benefit in those with sporadic pancreatic cancer.
- There is increased expression of MLH1 in vulvar carcinoma neoplasms.
- decreased expression in gastric mucosa during Helicobacter pylori gastritis
- The results of the splicing assay suggest that inclusion of exon 3 in the mRNA is exon splicing enhancer (ESE) dependent.
- Data show that hypermethylation of the MLH1 gene is occasionally involved in the pathogenesis of hematological malignancies, but is not always associated with microsatellite instability.
- We sequenced the MLH1/MSH2 coding and promoter core regions in patients with cancers suggestive of hereditary non-polyposis colorectal cancer, and correlated deleterious mutations with clinical and tumour features.
- No correlation between microsatellite instability and hMLH1, hMSH2 or P53 protein expression in basal cell carcinma was found.
- hMLH1 is the major altered mismatch repair gene involved in nonsmoking NSCLC tumorigenesis and promoter methylation is the predominant mechanism in hMLH1 and hMSH2 deregulation
- Microsatellite instability is linked to loss of hMLH1 expression in advanced gastric cancers
- This study investigates microsatellite instability in multiple primary colorectal cancers, and the relevance of MLH1, MSH2, and MSH6 gene expression in hereditary nonpolyposis colon cancer.
- High frequency and diverse spectrum of large genomic alterations in hMLH1 in suspected Lynch syndrome patients.
- A germline mutation of MLH1 gene could be found in patients with hereditary nonpolyposis colorectal cancer syndrome.
- Germline epimutations should be suspected in younger individuals without a family history who present with a microsatellite unstable tumor showing loss of MLH1 expression.
- The frequency of MSI (microsatellite instability) caused by hMLH1 promoter methylation increases with tumor progression in right-sided SCRCs.
- Weak to absent protein expression suggests RASSF1 and MLH1 post-transcription deregulation in monophasic synovial sarcoma.
- Data show that no genomic DNA fragment aberration of MLH1 gene was uncovered from 20 sporadic colorectal cancer.
- Results confirmed complete exon skipping for the mutations of MLH1 in hereditary nonpolyposis colorectal cancer patients.
- APC and K-ras, but not CTNNB1 mutations have roles in regulation of expression of hMLH1 in sporadic colorectal carcinomas
- Identification of a splicing enhancer in exon 17 of MLH1.
- analysis of MLH1 and MSH2 missense and silent mutations effect on aberrant splicing
- biochemical analysis of the MutLalpha. MutSalpha complex
- results demonstrate that the loss of expression of MLH-1 and MSH-2 might play a role in the pathogenesis and/or malignant transformation in some renal carcinomas
- We demonstrated an inverse relationship between hMLH1 promoter hypermethylation and MGMT promoter hypermethylation (P = 0.041), suggesting that a number of distinct hypermethylation-associated pathways may exist in colorectal cancer
- MLH1 is associated with longevity.
- It is concluded that the rare foci of hypermethylation of the MLH1 promoter in normal colon epithelium from people with colorectal cancer is associated with silencing of the gene that may play a role in the early evolution of these neoplasms.
- Alu is a promoting factor for the genomic recombinations in both MLH1 and MSH2, and the local Alu density may be involved in shaping the deletion pattern.
- Microsatellite instability and modifications in the hMLH1 and hMSH2 genes are implicated in a significant proportion of the patients with head and neck cancer.
- Hypermethylation of hMLH1 is associated with primary adenocarcinomas of the small bowel
- Study found that 40% of patients who were < or = 45 years of age at the time of diagnosis of colorectal cancer have tumors which are related to the absence of expression of either hMLH1 or hMSH2 genes.
- The high agreement between AIP and MLH1 gene promoter methylation 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.
- results indicate the P648S & L559R mutations from patients with suspected hereditary nonpolyposis colorectal cancer were pathogenic because they disrupted MLH1 protein interaction with its partner PMS2 in vitro & abolished MLH1 expression in HCT116 cells
- hMLH1 hypermethylation in tissue may be the primary event caused by endogenous/exogenous factors in esophageal diseases, aiding disease progression.
- HOXA5 is a transcriptional regulator of hMLH1 in breast cancer cells
- Our study, probably for the first time, showed through immunohistochemical detection of hMSH2 and hMLH1 gene that DNA MMR system does not play a prominent role in liver fluke infection-associated cholangiocarcinogenesis.
- hMSH2 and hMLH1 may have a role in development of secondary carcinoma in the gastrointestinal tract in patients (stomach and colorectal carcinoma)
- Variation in MLH1 distribution in recombination maps for individual chromosome in human testis.
- Germline mutations of hMLH1 and hMSH2 genes are identified in about one-third hereditary nonpolyposis colorectal cancer (HNPCC) kindreds fulfilling Chinese HNPCC criteria.
- Smoking promoted colorectal cancer in a dose-dependent manner in hMSH2 in males (P < 0.05). Females with hMSH2 mutations and both sexes with the hMLH1 groups only demonstrated a smoking effect after an extensive smoking history (P < 0.05).
- The inactivation of the DNA-mismatch-repair-gene MLH1 and microsatellite instability may play a minor role in somatic colorectal cancer development.
- The MLH1 RNA expression was correlated with microsatellite instability status and an inverse correlation was found between tumor MLH1 RNA expression and MLH1 DNA methylation.
- microsatellite instability and a loss of protein expression of DNA mismatch repair protein Mlh1 may be associated with the pathogenesis of sporadic endometrioid endometrial adenocarcinoma and might have a role as a prognostic parameter
- These results indicate that an age-related increase of medullary-type tumors in poorly differentiated adenocarcinoma may play an important role in the increase of absent hMLH1 expression and Microsatellite instability (MSI) in colorectal carcinoma.
- Missense mutations in MLH1 are likely to affect splicing only when located in weak alternative exons. When they do so, they might modulate in a tissue-specific manner cancer onset and its phenotypic manifestations.
- MLH1 394G-->C occurred exclusively in sporadic colorectal cancer patients.
- Hyperplastic polyps in patients with MSI-H were more likely to have loss of hMLH1 protein expression, suggesting that they may be an implortant precursor lesion in MSI-H colorectal carcinogenesis.
- The identification of residues whose mutation disrupts MutL-MutS interaction and affects mismatch repair activity, suggesting a mechanism by which hereditary mutations in this region can produce a cancer predisposition.
- In pstreplicative mismatch repair, this protein interacts wiwth MutL protein.
- Hyperplastic polyps in patients with MSI-H were more likely to have loss of hMLH1 protein expression, suggesting that they may be an implortant precursor lesion in MSI-H colorectal carcinogenesis.
- In three adenocarcinomas, microsatellite instability and lack of the MLH1 protein expression were detected.
- hMLH1 may have a role in development of secondary carcinoma in the gastrointestinal tract in patients (stomach and colorectal carcinoma)
- Inactivation of MLH1 gene is associated with head and neck squamous cell carcinoma tumors and leukoplakia
- Although the frequency is much lower than that of genomic deletions, there are partial gene duplications implicated in hereditary nonpolyposis colorectal cancer.
- Epigenetic silencing of MLH1 is associated with endometrial and colorectal cancers
- the patterns of somatic events (LOH and promoter methylation) differ depending on the tissue and germline mutation.
- Hypoxia induced coordinated repression of MLH1 and MSH2 leads to genetic instability and consequent tumor progression in cancer cells.
- Decrease of expression of hMLH1 was significantly correlated with methylation.
- Microsatellite instability with absent hMLH1 expression plays a role in the development of poorly differentiated adenocarcinoma and microsatellite-unstable mucinous carcinoma in the elderly.
- The MLH1 -93G>A polymorphism was associated with an increased risk of MSI-H colorectal cancer.
- MLH1 is required for signaling to the autophagic pathway after exposure to thioguanine.
- Two to six percent of CRC are caused by germline mutation in the mismatch repair genes MLH1, MSH2 and MSH6.
- Silencing the MLH1 gene expression by its promoter methylation stops the formation of MLH1 protein and activation of the DNA repair gene. This is a cause for genomic instability and cell proliferation to the point of colorectal cancer formation.
- Expression of hMSH2 and hMLH1 proteins was up-regulated in three cases, whereas in two cases that of hPMS2 was increased. hMSH6 expression was comparable to that of normal cells in all cases.
- genomic rearrangements of MLH1 and MSH6 in patients suspected of hereditary nonpolyposis colorectal cancer were studied using a new interphase FISH technique
- in hereditary non-polyposis colorectal cancer families, a proclivity to multiple tumours in the same subject & higher tumour burden per family were most relevant findings in affected patients with founder mutation compared to other MLH1 or MSH2 mutations
- While CDH1 methylation seems to be an early event in Hp gastritis, MLH1 methylation occurs late along with IM.
- The 101 MLH1 variants were examined for the dominant mutator effect by three yeast assays and for the ability of the variant to repair a heteroduplex DNA with mismatch bases by in vitro MMR assay.
- quantitative MLH1 methylation analysis in MSI-H CRC is a valuable molecular tool to distinguish between HNPCC and sporadic MSI-H CRC
- Previous studies may have wrongly estimated association between methylation of the MLH1 gene and the lack of its protein expression in colorectal cancers.
- Eighteen germline mutations (50%) were identified, 9 in MLH1 and 9 in MSH2, in Hungarian hereditary non-polyposis colorectal cancer (HNPCC) and suspected-HNPCC families.
- MLH1 hypermethylation was found in 16% of colonic polyps in young patients. It is an epigenetic change that may result in an accelerated progression to carcinoma.
- predicts a broader role for FANCJ in DNA damage signaling independent of BRCA1
- A panel of markers including at least RUNX3, CACNA1G, IGF2, and MLH1 can serve as a sensitive and specific marker panel for CIMP(Cpg island methylator phenotype)-high.
- No loss of nuclear expression of either hMLH1 or hMSH2 was identified in any cases of intraductal or invasive ductal carcinoma, suggesting that hMLH1 or hMSH2 may not play an essential role in the majority of cases of the breast carcinoma.
- The researchers found three germline mutations associated with the clinical phenotype of Lynch syndrome
- Expression may be reduced in some early gastric carcinomas.
- identified a C to G nucleotide substitution at position -107 relative to the MLH1 gene translation initiation site in three of 163 colorectal cancer patients with an allele frequency of 0.0092 (3/326)
- an abnormal mismatch repair (one component of mismatch repair is MLH1 protein) may contribute to the carcinogenesis of a subset of laryngeal squamous cell carcinoma
- Left-sided microsatellite unstable colorectal cancers show significantly less frequent methylation of hMLH1.
- hMLH1 rs1799977 polymorphism may contribute to the etiology of early-onset lung cancer as well as some specific subtype of lung cancer.
- Decreased expression of hMLH1 correlates with reduced 5-fluorouracil-mediated apoptosis in colon cancer cells
- a common substitution in the basal promoter of MLH1 (position -93, rs1800734) modifies the risk of cancer after methylating chemotherapy
- Our results show that hMLH1 interacts with Tbeta4 and regulates its expression and nuclear transport.
- results show methylation of MLH1 promoter doesn't exclude presence of germline mutation in mismatch repair gene; hypermethylation of MLH1 promoter may be present in most cases of sporadic colorectal cancer but does not exclude diagnosis of Lynch syndrome
- lack of association between MLH1 protein expression and Microsatellite instability in endometrial cancer samples was observed
- silencing of the three transcription start sites in the bidirectional MLH1 promoter CpG island in cancer cells involves distinct changes in nucleosomal occupancy
- Mutant L Homologue 1 (MLH1) is a possible new immunohistochemical marker for prostatic cancer.
- Association between mutation in the hMLH1 gene and the risk of extracolonic neoplasms.
- Low expression of hMLH1 in esophageal squamous cell carcinomas is a potential marker of tumor response to chemoradiotherapy and survival.
- a mutation in the MLH1 3'-untranslated region confers a mutator phenotype and mismatch repair deficiency in patients with relapsed leukemia
- The two novel germline mutations of MLH1 in hereditary non-polyposis colorectal cancer families i.e. CGC right arrow TGC at codon 217 of exon 8 and CCG right arrow CTG at codon 581 of exon 16, are very likely to have pathological significance.
- This work availably evaluated the functional consequences of some missense mutations not previously determined in the hMLH1 gene and might be useful for the clinical diagnosis of hereditary gastrointestinal cancer, especially in East Asians
- aberrant Fhit and Mlh1 expression could be related to colorectal carcinoma de novo (DN) carcinogenesis.
- Poorly differentiated colorectal adenocarcinomas strongly correlates with miscrosatellite instability and methylation of the p16 and hMLH1 promoter region.
- Examined association between MTHFR/thymidylate synthase gene polymorphisms and methylation of p16(INK4A) and hMLH1 genes in spontaneously aborted embryos with normal chromosomal integrity.
- In an epigenetic aspect, both MACS and MSI+ had a high rate of CpG island methylator phenotype (46.2 and 42.9%). However, they differed in the presence of hMLH1 methylation (7.7 vs 57.1%, p < 0.05).
- The MLH1 I219V alteration does not directly contribute to the etiology of UC through an impairment of mismatch repair.
- These results support the evidence that hMSH2 and hMLH1 expression may increase prior to gastric cancer.
- These results demonstrate that the MLH1 variants significantly decrease the stability of the protein, while another missense variant is able to compromise heterodimerization of the MLH1-PMS2 complex.
- Adenine nucleotides induce large asymmetric conformational changes in full-length human MutL alpha. These changes are associated with significant increases in secondary structure.
- Expression of MLH1 protein was significantly lower in patients with gastric cancer showing a high frequency of microsatellite instability.
- In about 90-95% of the cases, germline mutations of the hMLH1 or hMSH2 genes can be demonstrated, while only a low percentage is caused by the mutations of hMSH6, hPMS1 and hPMS2.
- The left-sided preponderance of DNA mismatch repair defective colorectal carcinomas was mostly associated with hMLH1, and with possible loss of hMSH2 expression.
- These findings provide strong evidence that MLH1 promoter methylation in normal body cells mimics Colorectal Neoplasms, Hereditary Nonpolyposis and constitutes a pathogenic pre-lesion in MLH1.
- loss of function of hMLH1 and hMSH2 is not involved in sporadic RCC, either by promoter methylation or mutation in their exons. LOH showed that chromosomal instability of large fragments of DNA was the main genetic alteration detected associated with RCC
- The histological grade of malignancy interferes in hMLH1 immunoexpression; however, hMLH1 overexpression was correlated and associated with well-differentiated oral squamous cell carcinoma.
- Folate intake and tumors harboring BRAF mutations and between vitamin B6 intake and those showing MLH1 hypermethylation were associated with colorectal cancer
- MLH1 is transcriptionally repressed by the hypoxia-inducible transcription factors, DEC1 and DEC2.
- Analysis of 38 hMLH1 missense mutations showed that the majority of mutations caused significant (>50%) reductions in their interaction with hMRE11.
- The novel mutations c.243_244insA in MLH1 gene and c.1215_1218dupCCGA in MSH2 gene were the disease-causing mutations in the two HNPCC families.
- The G>A nt-93 variant of the MLH1 gene is associated with an increased risk of invasive ovarian cancer.
- aberrant methylation of the hMLH1 gene may play a role in BRAF mutation-promoted thyroid tumorigenesis
- MMR-dependent intrinsic apoptosis is p53-independent, but stimulated by hMLH1/c-Abl/p73alpha/GADD45alpha retrograde signaling
- These data suggest that the hMLH1 mRNA quantitation in colorectal cancer cells may be helpful for evaluating the prognosis of CRC patients receiving 5-FU-based adjuvant chemotherapy after a surgical resection.
- The total mutation rate of hMLH1 and hMSH2 gene in Chinese and Korean hereditary nonpolyposis colorectal cancer was similar and lower than that reported in Western countries. But the mutation characteristics were different in the two populations.
- High linkage disequilibrium in the genomic regions covering hMLH1, indicate that common genetic variants in general are not involved in the development of sporadic colorectal cancer
- MLH1 promoter methylation is associated with colorectal and endometrial carcinomas
- A total of 22 unclassified variants in the mismatch repair genes MLH1 and MSH2 involved in hereditary nonpolyposis colorectal cancer out of 85different variant alleles examined in 82 families affected splicing.
- In the normal tissues of hereditary non-polyposis colorectal cancer patients with MSH2 mutations, the MLH1/MSH2 transcript ratios were significantly elevated as compared to the ratios of normal mucosa in patients with MMR-proficient tumours.
- Microsatellite instability and loss of MLH1 expression was rare, suggesting that MLH1 promoter methylation does not usually lead to gene silencing in lung cancer.
- The MLH1 -93 G>A promoter polymorphism was associated with CpG island methylator phenotype in colon cancer.
- MLH1 hypermethylation is reduntanly associated with colorectal cancers of Lynch-syndrome patients.
- An analysis of MMR genes may be useful for patients with endometrial cancer showing familial aggregation
- No significant effects of MLH1 -93A/G polymorphisms was seen on the initial repair of MMS-induced DNA damage in human lymphocytes.
- significant correlation was observed among the scores for the proteins. CONCLUSIONS: The expressions of hMLH1 and hMSH2 are independently regulated and play different roles in NSCLC.
- All of the KRAS-mutant Microsatellite instability (MSI)-H (high) tumors harbored sequence alterations MLH1, which implies that KRAS mutation more frequently and almost exclusively occurs in DNA mismatch repair gene-mutant MSI-H tumors.
- In this large study of mismatch repair gene mutation carriers in the United States, MLH1 carriers had more colorectal neoplasms than MSH2 carriers, endometrial cancer prevalence was similar.
- findings suggest that the MLH1 -93G>A polymorphism defines a low penetrance risk allele for colorectal cancer
- Eight hMSH2 or hMLH1 gene sequence variations were found in 12 Chinese families with hereditary nonpolyposis colorectal cancer (HNPCC).
- expression status of mismatched repair genes hMLH1, the incidence of microsatellite instability high colorectal cancer in populations based study.
- SNP-based method for detecting LOH in MLH1 and MSH2 is simple to perform with instruments available in most clinical genetics laboratories
- MLH1-deficient human cells are more resistant to psoralen ICLs (DNA interstrand crosslinks ), in contrast to the sensitivity to these lesions displayed by MSH2-deficient cells
- hMLH1-deficient cell lines due to either epigenetic silencing or mutation showed very similar IC(50) and were four- to nine-fold more sensitive to CPT-11 than the MSS line
- microsatellite instability Colorectal cancer patients with low Bcl-2 and hMLH1 and hMSH2 demonstrate a significantly shorter disease-free survival.
- MLH1 methylation was observed in 60% of population-based MSI-H tumors and 13% of clinic-based colorectal tumors.
- Calretinin, MLH-1, and CDX2 may help to differentiate medullary carcinoma from poorly differentiated colonic carcinoma of the colon.
- The site S2 in Mlh1 mediates Exo1 recruitment in order to optimize mismatch repair-dependent mutation avoidance.
- Frequent alterations of MLH1 at chromosomal 3p22.3 region in early and late-onset breast cancer are reported with reference to clinical and prognostic significance.
- interactions between DNA repair genes hMLH1, APEX1, MGMT, XRCC1 and XPD and electric transformers and power line distances from the houses of childhood acute leukemia patients revealed gene-environment interaction existed with XRCC1 Ex9+16 A allele
- Three novel hereditary nonpolyposis colorectal cancer mutations are reported in Korean families. MLH1 has a frameshift mutation and a premature stop codon.
- Extensive promoter methylation was associated with MLH1 inactivation, microsatellite instability, and BRAF mutation in sporadic colorectal cancers.
- The G67E mutation in hMLH1 is associated with an unusual presentation of Lynch syndrome
- Deficient mismatch repair system caused by hypermethylation of the MLH1 promoter is associated with sporadic advanced colorectal cancer
- The immunohistochemical expression of hMLH1 and hMSH2 proteins in ovarian cancer has no predictive value in resistance to cisplatin.