MLH1

Summary

Gene Symbol: MLH1
Description: mutL homolog 1
Alias: COCA2, FCC2, HNPCC, HNPCC2, hMLH1, DNA mismatch repair protein Mlh1, mutL homolog 1, colon cancer, nonpolyposis type 2
Species: human
Products:     MLH1

Top Publications

  1. Arnold S, Buchanan D, Barker M, Jaskowski L, Walsh M, Birney G, et al. Classifying MLH1 and MSH2 variants using bioinformatic prediction, splicing assays, segregation, and tumor characteristics. Hum Mutat. 2009;30:757-70 pubmed publisher
    ..Six programs were used to predict the effect of 13 MLH1 and 6 MSH2 gene variants on pre-mRNA splicing...
  2. Koessler T, Oestergaard M, Song H, Tyrer J, Perkins B, Dunning A, et al. Common variants in mismatch repair genes and risk of colorectal cancer. Gut. 2008;57:1097-101 pubmed publisher
    ..A total of 2299 cases and 2284 unrelated controls were genotyped for 68 tagging SNPs in seven MMR genes (MLH1, MLH3, MSH2, MSH3, MSH6, PMS1 and PMS2)...
  3. Williams S, Wilson J, Clark A, Mitson Salazar A, Tomashevski A, Ananth S, et al. Functional and physical interaction between the mismatch repair and FA-BRCA pathways. Hum Mol Genet. 2011;20:4395-410 pubmed publisher
    ..Here we show that FANCD2 interacts with the MMR proteins MSH2 and MLH1. FANCD2 monoubiquitylation, foci formation and chromatin loading are greatly diminished in MSH2-deficient cells...
  4. Yoon S, Park T, Kim N, Lee K, Kim J, Song J, et al. Three new nonsense mutations of MLH1 and MSH2 genes in Korean families with hereditary nonpolyposis colorectal cancer. Cancer Genet Cytogenet. 2009;188:61-4 pubmed publisher
    Hereditary nonpolyposis colorectal cancer (HNPCC) (MIM #114500), also called Lynch syndrome, is an autosomal dominantly inherited cancer syndrome accounting for 1-5% of all colorectal cancer cases...
  5. Lee K, Lee J, Nam J, Choi C, Lee M, Park C, et al. Promoter methylation status of hMLH1, hMSH2, and MGMT genes in colorectal cancer associated with adenoma-carcinoma sequence. Langenbecks Arch Surg. 2011;396:1017-26 pubmed publisher
    ..The aim of this study was to investigate the methylation status of MutL homolog 1 (hMLH1), MutS homolog 2 (hMSH2), and O-6-methylguanine-DNA methyltransferase (MGMT) in a series of colorectal carcinomas ..
  6. Betz B, Theiss S, Aktas M, Konermann C, Goecke T, Möslein G, et al. Comparative in silico analyses and experimental validation of novel splice site and missense mutations in the genes MLH1 and MSH2. J Cancer Res Clin Oncol. 2010;136:123-34 pubmed publisher
    ..colorectal cancer and other malignancies, is caused by inactivating mutations of DNA mismatch repair genes, mainly MLH1 and MSH2...
  7. Bujalkova M, Zavodna K, Krivulcik T, Ilencikova D, Wolf B, Kovac M, et al. Multiplex SNaPshot genotyping for detecting loss of heterozygosity in the mismatch-repair genes MLH1 and MSH2 in microsatellite-unstable tumors. Clin Chem. 2008;54:1844-54 pubmed publisher
    In the workup of patients with suspected hereditary nonpolyposis colorectal cancer (HNPCC), detection of loss of heterozygosity (LOH) could help pinpoint the mismatch-repair (MMR) gene carrying the germline mutation, but analysis of ..
  8. Li L, Morales J, Hwang A, Wagner M, Boothman D. DNA mismatch repair-dependent activation of c-Abl/p73alpha/GADD45alpha-mediated apoptosis. J Biol Chem. 2008;283:21394-403 pubmed publisher
    ..Thus, MMR-dependent intrinsic apoptosis is p53-independent, but stimulated by hMLH1/c-Abl/p73alpha/GADD45alpha retrograde signaling.
  9. Pan X, Yang W, Xu G, Bai P, Qin H, Zhang L, et al. The association between MLH1 -93 G>A polymorphism of DNA mismatch repair and cancer susceptibility: a meta-analysis. Mutagenesis. 2011;26:667-73 pubmed publisher
    ..Polymorphisms of MLH1 in individuals may have an effect on the DNA repair capacity and therefore on cancer risk...

More Information

Publications86

  1. Jin H, Liu X, Li V, Ding Y, Yang B, Geng J, et al. Detection of mismatch repair gene germline mutation carrier among Chinese population with colorectal cancer. BMC Cancer. 2008;8:44 pubmed publisher
    Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant syndrome. The National Cancer Institute (NCI) has recommended the Revised Bethesda guidelines for screening HNPCC...
  2. Seng T, Currey N, Cooper W, Lee C, Chan C, Horvath L, et al. DLEC1 and MLH1 promoter methylation are associated with poor prognosis in non-small cell lung carcinoma. Br J Cancer. 2008;99:375-82 pubmed publisher
    ..This study set out to investigate promoter methylation in the deleted in lung and oesophageal cancer 1 (DLEC1), MLH1 and other 3p genes in 239 non-small cell lung carcinomas (NSCLC). DLEC1 was methylated in 38.7%, MLH1 in 35...
  3. Xu J, Yin Z, Huang M, Wang X, Gao W, Liu L, et al. MLH1 polymorphisms and cancer risk: a meta-analysis based on 33 case-control studies. Asian Pac J Cancer Prev. 2012;13:901-7 pubmed
    Cumulative evidence suggests that MLH1, the key component in the mismatch pathway, plays an important role in human cancers. Two potential functional polymorphisms (-93G>A and I219V) of MLH1 have been implicated in cancer risk...
  4. Bischoff J, Ignatov A, Semczuk A, Schwarzenau C, Ignatov T, Krebs T, et al. hMLH1 promoter hypermethylation and MSI status in human endometrial carcinomas with and without metastases. Clin Exp Metastasis. 2012;29:889-900 pubmed publisher
    We investigated the methylation status of mismatch repair gene hMLH1 in 80 primary human endometrial carcinomas (ECs) and in 30 metastatic lesions...
  5. Stubbert L, Smith J, McKay B. Decreased transcription-coupled nucleotide excision repair capacity is associated with increased p53- and MLH1-independent apoptosis in response to cisplatin. BMC Cancer. 2010;10:207 pubmed publisher
    ..These results further suggest that CSB represents a potential target for cancer therapy that may be important to overcome resistance to cisplatin in the clinic. ..
  6. Vilkin A, Niv Y, Nagasaka T, Morgenstern S, Levi Z, Fireman Z, et al. Microsatellite instability, MLH1 promoter methylation, and BRAF mutation analysis in sporadic colorectal cancers of different ethnic groups in Israel. Cancer. 2009;115:760-9 pubmed publisher
    ..MSI analysis, mutL homolog 1 (MLH1) and mutS homolog 2 (MSH2) protein expression levels, and MLH1 promoter methylation were investigated by combined ..
  7. Mann A, Hogdall E, Ramus S, Dicioccio R, Hogdall C, Quaye L, et al. Mismatch repair gene polymorphisms and survival in invasive ovarian cancer patients. Eur J Cancer. 2008;44:2259-65 pubmed publisher
    ..05) in seven MMR genes (MLH1, MLH3, MSH2, MSH3, MSH6, PMS1 and PMS2) and survival of invasive ovarian cancer patients in three case-control ..
  8. Campbell P, Curtin K, Ulrich C, Samowitz W, Bigler J, Velicer C, et al. Mismatch repair polymorphisms and risk of colon cancer, tumour microsatellite instability and interactions with lifestyle factors. Gut. 2009;58:661-7 pubmed publisher
    ..A study was conducted to examine whether MLH1 (-93G>A and Ile219Val) and MSH6 (Gly39Glu) polymorphisms were associated with risk of colon cancer in data from ..
  9. Jarvinen H, Renkonen Sinisalo L, Aktan Collan K, Peltomaki P, Aaltonen L, Mecklin J. Ten years after mutation testing for Lynch syndrome: cancer incidence and outcome in mutation-positive and mutation-negative family members. J Clin Oncol. 2009;27:4793-7 pubmed publisher
    ..The long-term effectiveness of surveillance was evaluated in Lynch syndrome family members tested approximately 10 years ago...
  10. Donehower L, Creighton C, Schultz N, Shinbrot E, Chang K, Gunaratne P, et al. MLH1-silenced and non-silenced subgroups of hypermutated colorectal carcinomas have distinct mutational landscapes. J Pathol. 2013;229:99-110 pubmed publisher
    ..unlike the majority of colorectal carcinomas, are often diploid, exhibit frequent epigenetic silencing of the MLH1 DNA mismatch repair gene, and have a better clinical prognosis...
  11. Gay L, Arends M, Mitrou P, Bowman R, Ibrahim A, Happerfield L, et al. MLH1 promoter methylation, diet, and lifestyle factors in mismatch repair deficient colorectal cancer patients from EPIC-Norfolk. Nutr Cancer. 2011;63:1000-10 pubmed publisher
    ..Tumor samples from 185 individuals in the EPIC-Norfolk study were analyzed for MLH1 gene promoter methylation and microsatellite instability (MSI)...
  12. van der Post R, Kiemeney L, Ligtenberg M, Witjes J, Hulsbergen van de Kaa C, Bodmer D, et al. Risk of urothelial bladder cancer in Lynch syndrome is increased, in particular among MSH2 mutation carriers. J Med Genet. 2010;47:464-70 pubmed publisher
    ..and upper urinary tract tumours are characteristic for Lynch syndrome (hereditary non-polyposis colon carcinoma, HNPCC)...
  13. Fan Y, Wang W, Zhu M, Zhou J, Peng J, Xu L, et al. Analysis of hMLH1 missense mutations in East Asian patients with suspected hereditary nonpolyposis colorectal cancer. Clin Cancer Res. 2007;13:7515-21 pubmed
    Germ line mutations in the DNA mismatch repair gene hMLH1 are a frequent cause of hereditary nonpolyposis colorectal cancer and about one-third of these are missense mutations...
  14. Goel A, Nguyen T, Leung H, Nagasaka T, Rhees J, Hotchkiss E, et al. De novo constitutional MLH1 epimutations confer early-onset colorectal cancer in two new sporadic Lynch syndrome cases, with derivation of the epimutation on the paternal allele in one. Int J Cancer. 2011;128:869-78 pubmed publisher
    ..dominant cancer predisposition syndrome classically caused by germline mutations of the mismatch repair genes, MLH1, MSH2, MSH6 and PMS2...
  15. Grindedal E, Møller P, Eeles R, Stormorken A, Bowitz Lothe I, Landrø S, et al. Germ-line mutations in mismatch repair genes associated with prostate cancer. Cancer Epidemiol Biomarkers Prev. 2009;18:2460-7 pubmed publisher
    ..The mismatch repair (MMR) genes MLH1, MSH2, MSH6, and PMS2 are associated with Lynch syndrome where colon and endometrial cancers are the predominant ..
  16. Stoffel E, Mukherjee B, Raymond V, Tayob N, Kastrinos F, Sparr J, et al. Calculation of risk of colorectal and endometrial cancer among patients with Lynch syndrome. Gastroenterology. 2009;137:1621-7 pubmed publisher
    ..We studied 147 families with mismatch repair gene mutations (55 MLH1, 81 MSH2, and 11 MSH6) identified at 2 US cancer genetics clinics...
  17. Kwok C, Ward R, Hawkins N, Hitchins M. Detection of allelic imbalance in MLH1 expression by pyrosequencing serves as a tool for the identification of germline defects in Lynch syndrome. Fam Cancer. 2010;9:345-56 pubmed publisher
    ..syndrome is caused by germline heterozygous loss-of-function sequence mutations within the mismatch repair genes MLH1, MSH2, MSH6 or PMS2...
  18. Crepin M, Dieu M, Lejeune S, Escande F, Boidin D, Porchet N, et al. Evidence of constitutional MLH1 epimutation associated to transgenerational inheritance of cancer susceptibility. Hum Mutat. 2012;33:180-8 pubmed publisher
    ..Lynch syndrome-suspected patients without MMR germline mutation was screened for constitutional epimutations of MLH1 and MSH2 by quantitative bisulfite pyrosequencing...
  19. Tulupova E, Kumar R, Hanova M, Slyskova J, Pardini B, Polakova V, et al. Do polymorphisms and haplotypes of mismatch repair genes modulate risk of sporadic colorectal cancer?. Mutat Res. 2008;648:40-5 pubmed publisher
    ..34; 95% CI 1.03-1.74). The carriers of the variant allele for the polymorphism IVS9-1406C>T in hMLH1 exhibited a decreased risk of rectal cancer (OR 0.71; 95% CI 0.51-0.98)...
  20. Allan J, Shorto J, Adlard J, Bury J, Coggins R, George R, et al. MLH1 -93G>A promoter polymorphism and risk of mismatch repair deficient colorectal cancer. Int J Cancer. 2008;123:2456-9 pubmed publisher
    Rare inherited mutations in the mutL homolog 1 (MLH1) DNA mismatch repair gene can confer an increased susceptibility to colorectal cancer (CRC) with high penetrance where disease frequently develops in the proximal colon...
  21. Yap H, Chieng W, Lim J, Lim R, Soo R, Guo J, et al. Recurring MLH1 deleterious mutations in unrelated Chinese Lynch syndrome families in Singapore. Fam Cancer. 2009;8:85-94 pubmed publisher
    ..Families with clinical diagnosis of HNPCC (i.e...
  22. Stark A, Doukas A, Hugo H, Mehdorn H. The expression of mismatch repair proteins MLH1, MSH2 and MSH6 correlates with the Ki67 proliferation index and survival in patients with recurrent glioblastoma. Neurol Res. 2010;32:816-20 pubmed publisher
    ..We examined the protein expression of MLH1, MSH2 and MSH6 in paired initial and recurrent glioblastoma and compared the results to the Ki67 proliferation ..
  23. Sheng J, Fu L, Sun Z, Huang J, Han M, Mu H, et al. Mismatch repair gene mutations in Chinese HNPCC patients. Cytogenet Genome Res. 2008;122:22-7 pubmed publisher
    ..of DNA mismatch repair gene mutations in Chinese patients with hereditary non-polyposis colorectal cancer (HNPCC) or Lynch syndrome, the MLH1 and MSH2 genes from probands of 76 HNPCC families were sequenced...
  24. Langeberg W, Kwon E, Koopmeiners J, Ostrander E, Stanford J. Population-based study of the association of variants in mismatch repair genes with prostate cancer risk and outcomes. Cancer Epidemiol Biomarkers Prev. 2010;19:258-64 pubmed publisher
    ..Nineteen SNPs were evaluated in the key MMR genes: five in MLH1, 10 in MSH2, and 4 in PMS2...
  25. Shih C, Chen C, Lee I, Kao W, Wang Y. A polymorphism in the hMLH1 gene (-93G-->A) associated with lung cancer susceptibility and prognosis. Int J Mol Med. 2010;25:165-70 pubmed
    ..We investigated the association between the -93G-->A polymorphism in the mismatch repair hMLH1 gene for its role in the susceptibility and survival of non-small cell lung cancer (NSCLC) patients...
  26. Perez Carbonell L, Alenda C, Paya A, Castillejo A, Barbera V, Guillen C, et al. Methylation analysis of MLH1 improves the selection of patients for genetic testing in Lynch syndrome. J Mol Diagn. 2010;12:498-504 pubmed publisher
    Inactivation of MLH1 due to promoter hypermethylation strongly suggests a sporadic origin, providing exclusion criteria for Lynch syndrome...
  27. Stoehr C, Burger M, Stoehr R, Bertz S, Ruemmele P, Hofstaedter F, et al. Mismatch repair proteins hMLH1 and hMSH2 are differently expressed in the three main subtypes of sporadic renal cell carcinoma. Pathobiology. 2012;79:162-8 pubmed publisher
    We studied the role of minor mismatch repair proteins (MMR) human MutL homologue 1 (hMLH1) and human MutS homologue 2 (hMSH2) in the main subtypes of renal cell carcinoma (RCC)...
  28. Czerninski R, Krichevsky S, Ashhab Y, Gazit D, Patel V, Ben Yehuda D. Promoter hypermethylation of mismatch repair genes, hMLH1 and hMSH2 in oral squamous cell carcinoma. Oral Dis. 2009;15:206-13 pubmed publisher
    ..We therefore wanted to test whether hypermethylation of MMR genes (hMLH1, hMSH2) could contribute to oral carcinogenesis by correlating the information to patient clinical data...
  29. Julie C, Tresallet C, Brouquet A, Vallot C, Zimmermann U, Mitry E, et al. Identification in daily practice of patients with Lynch syndrome (hereditary nonpolyposis colorectal cancer): revised Bethesda guidelines-based approach versus molecular screening. Am J Gastroenterol. 2008;103:2825-35; quiz 2836 pubmed publisher
    The identification of individuals who should undergo hereditary nonpolyposis colorectal cancer (HNPCC) genetic testing remains a critical issue...
  30. Wang C, Zhou X, Zhang T, Xu Y, Cai S, Shi D. Two novel germline mutations of MLH1 and investigation of their pathobiology in hereditary non-polyposis colorectal cancer families in China. World J Gastroenterol. 2007;13:6254-8 pubmed
    ..microsatellite instability and expression of MLH1 in tumor tissues of hereditary non-polyposis colorectal cancer (HNPCC) with two novel germline mutations, and further investigate the pathobiology of the two novel mutations of MLH1...
  31. Morak M, Koehler U, Schackert H, Steinke V, Royer Pokora B, Schulmann K, et al. Biallelic MLH1 SNP cDNA expression or constitutional promoter methylation can hide genomic rearrangements causing Lynch syndrome. J Med Genet. 2011;48:513-9 pubmed publisher
    ..was performed to search for genomic imbalances in patients with suspected mutation-negative Lynch syndrome with MLH1 deficiency in their colorectal tumours...
  32. Niessen R, Kleibeuker J, Westers H, Jager P, Rozeveld D, Bos K, et al. PMS2 involvement in patients suspected of Lynch syndrome. Genes Chromosomes Cancer. 2009;48:322-9 pubmed publisher
    It is well-established that germline mutations in the mismatch repair genes MLH1, MSH2, and MSH6 cause Lynch syndrome. However, mutations in these three genes do not account for all Lynch syndrome (suspected) families...
  33. Kosinski J, Hinrichsen I, Bujnicki J, Friedhoff P, Plotz G. Identification of Lynch syndrome mutations in the MLH1-PMS2 interface that disturb dimerization and mismatch repair. Hum Mutat. 2010;31:975-82 pubmed publisher
    Missense alterations of the mismatch repair gene MLH1 have been identified in a significant proportion of individuals suspected of having Lynch syndrome, a hereditary syndrome that predisposes for cancer of colon and endometrium...
  34. Jin P, Lu X, Sheng J, Fu L, Meng X, Wang X, et al. Estrogen stimulates the expression of mismatch repair gene hMLH1 in colonic epithelial cells. Cancer Prev Res (Phila). 2010;3:910-6 pubmed publisher
    ..In cultured COLO205 cells, the effect of estradiol (E2) and antagonist ICI182.780 on the expression of hMLH1 and hMSH2 was studied using reverse transcription-PCR and Western blotting...
  35. Menigatti M, Truninger K, Gebbers J, Marbet U, Marra G, Schär P. Normal colorectal mucosa exhibits sex- and segment-specific susceptibility to DNA methylation at the hMLH1 and MGMT promoters. Oncogene. 2009;28:899-909 pubmed publisher
    ..and rectal mucosa collected from 100 healthy individuals undergoing screening colonoscopy were analysed for hMLH1 and MGMT promoter methylation with a quantitative PCR assay...
  36. Barrow E, Robinson L, Alduaij W, Shenton A, Clancy T, Lalloo F, et al. Cumulative lifetime incidence of extracolonic cancers in Lynch syndrome: a report of 121 families with proven mutations. Clin Genet. 2009;75:141-9 pubmed publisher
    ..0003). Gastric cancer risk in those born after 1935 does not justify surveillance. These penetrance estimates have been corrected for ascertainment bias and are appropriate for those referred to a high-risk clinic...
  37. Samowitz W, Curtin K, Wolff R, Albertsen H, Sweeney C, Caan B, et al. The MLH1 -93 G>A promoter polymorphism and genetic and epigenetic alterations in colon cancer. Genes Chromosomes Cancer. 2008;47:835-44 pubmed publisher
    The MLH1 -93 G>A promoter polymorphism has been reported to be associated with an increased risk of microsatellite unstable colorectal cancer...
  38. Xie J, Litman R, Wang S, Peng M, Guillemette S, Rooney T, et al. Targeting the FANCJ-BRCA1 interaction promotes a switch from recombination to poleta-dependent bypass. Oncogene. 2010;29:2499-508 pubmed publisher
    ..the poleta-dependent bypass promoted by FANCJ requires the direct binding to the mismatch repair (MMR) protein, MLH1. Together, our findings implicate that in human cells BRCA1 binding to FANCJ is critical to regulate DNA repair ..
  39. Li M, Liu L, Wang Z, Wang L, Liu Z, Xu G, et al. Overexpression of hMSH2 and hMLH1 protein in certain gastric cancers and their surrounding mucosae. Oncol Rep. 2008;19:401-6 pubmed
    ..is closely related to oncogenesis, which is usually accompanied with the loss of expression of hMSH2 and/or hMLH1. These two proteins are detected in many gastric cancers (GCs), and even their overexpression have been reported ..
  40. Wong J, Hawkins N, Ward R, Hitchins M. Methylation of the 3p22 region encompassing MLH1 is representative of the CpG island methylator phenotype in colorectal cancer. Mod Pathol. 2011;24:396-411 pubmed publisher
    ..We previously reported the concurrent methylation of the mismatch repair gene MLH1 with a cluster of flanking genes in chromosome region 3p22 in sporadic colorectal carcinoma exhibiting ..
  41. Bonadona V, Bonaïti B, Olschwang S, Grandjouan S, Huiart L, Longy M, et al. Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome. JAMA. 2011;305:2304-10 pubmed publisher
    ..age-specific cumulative risks of developing various tumors using a large series of families with mutations of the MLH1, MSH2, and MSH6 genes...
  42. de Vogel S, Weijenberg M, Herman J, Wouters K, de Goeij A, van den Brandt P, et al. MGMT and MLH1 promoter methylation versus APC, KRAS and BRAF gene mutations in colorectal cancer: indications for distinct pathways and sequence of events. Ann Oncol. 2009;20:1216-22 pubmed publisher
    ..cancer (CRC), we investigated whether O6-methylguanine DNA methyltransferase (MGMT) and Human Mut-L Homologue 1 (MLH1) promoter hypermethylation are associated with APC, KRAS and BRAF mutations among 734 CRC patients...
  43. Wei W, Liu L, Chen J, Jin K, Jiang F, Liu F, et al. Racial differences in MLH1 and MSH2 mutation: an analysis of yellow race and white race based on the InSiGHT database. J Bioinform Comput Biol. 2010;8 Suppl 1:111-25 pubmed
    MLH1 and MSH2 mutations underlie 90% of hereditary nonpolyposis colorectal cancer (HNPCC) mutations...
  44. Hitchins M, Owens S, Kwok C, Godsmark G, Algar U, Ramesar R. Identification of new cases of early-onset colorectal cancer with an MLH1 epimutation in an ethnically diverse South African cohort. Clin Genet. 2011;80:428-34 pubmed publisher
    ..endometrial and other cancers, is caused by germline mutations of the mismatch repair genes, most commonly MLH1, MSH2 and MSH6...
  45. Mei M, Liu D, Dong S, Ingvarsson S, Goodfellow P, Chen H. The MLH1 -93 promoter variant influences gene expression. Cancer Epidemiol. 2010;34:93-5 pubmed publisher
    The -93 SNP of MLH1 gene is associated with MLH1 gene methylation in endometrial and colorectal cancers...
  46. Hitchins M, Rapkins R, Kwok C, Srivastava S, Wong J, Khachigian L, et al. Dominantly inherited constitutional epigenetic silencing of MLH1 in a cancer-affected family is linked to a single nucleotide variant within the 5'UTR. Cancer Cell. 2011;20:200-13 pubmed publisher
    ..Constitutional MLH1 epimutations occur in individuals with young-onset cancer and demonstrate non-Mendelian inheritance through their ..
  47. Kanao R, Hanaoka F, Masutani C. A novel interaction between human DNA polymerase eta and MutLalpha. Biochem Biophys Res Commun. 2009;389:40-5 pubmed publisher
    ..Here, we identified human MLH1, an essential component of mismatch repair (MMR), as a Poleta-interacting protein...
  48. Wang J, Sasco A, Fu C, Xue H, Guo G, Hua Z, et al. Aberrant DNA methylation of P16, MGMT, and hMLH1 genes in combination with MTHFR C677T genetic polymorphism in esophageal squamous cell carcinoma. Cancer Epidemiol Biomarkers Prev. 2008;17:118-25 pubmed publisher
    To explore the role of aberrant hypermethylation of cancer-related genes, such as P16, MGMT, and hMLH1, in the esophageal squamous cell carcinoma (ESCC) as well as its relation to dietary folate intake and MTHFR C677T polymorphism, we ..
  49. Kastrinos F, Stoffel E, Balmana J, Steyerberg E, Mercado R, Syngal S. Phenotype comparison of MLH1 and MSH2 mutation carriers in a cohort of 1,914 individuals undergoing clinical genetic testing in the United States. Cancer Epidemiol Biomarkers Prev. 2008;17:2044-51 pubmed publisher
    Lynch syndrome is caused by germ-line mismatch repair gene mutations. We examined the phenotypic differences between MLH1 and MSH2 gene mutation carriers and whether mutation type (point versus large rearrangement) affected phenotypic ..
  50. Barrow E, Alduaij W, Robinson L, Shenton A, Clancy T, Lalloo F, et al. Colorectal cancer in HNPCC: cumulative lifetime incidence, survival and tumour distribution. A report of 121 families with proven mutations. Clin Genet. 2008;74:233-42 pubmed publisher
    Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant condition caused by inactivating mutations of DNA mismatch repair (MMR) genes...
  51. Zhou H, Yan S, Zhou X, Du X, Zhang T, Cai X, et al. MLH1 promoter germline-methylation in selected probands of Chinese hereditary non-polyposis colorectal cancer families. World J Gastroenterol. 2008;14:7329-34 pubmed
    ..the MLH1 gene promoter germline-methylation in probands of Chinese hereditary nonpolyposis colorectal cancer (HNPCC), and to evaluate the role of methylation in MLH1 gene promoter and molecular genetics in screening for HNPCC...
  52. Huang Q, Huang J, Zhang B, Baum L, Fu W. Methylation variable position profiles of hMLH1 promoter CpG islands in human sporadic colorectal carcinoma. Diagn Mol Pathol. 2012;21:24-33 pubmed publisher
    Aberrant hypermethylation of CpG islands (CGIs) in hMLH1 promoter regions has been well known to play an important role in the tumorigenesis of human sporadic colorectal carcinoma (SCRC)...
  53. Zhao N, Zhu F, Yuan F, Haick A, Fukushige S, Gu L, et al. The interplay between hMLH1 and hMRE11: role in MMR and the effect of hMLH1 mutations. Biochem Biophys Res Commun. 2008;370:338-43 pubmed publisher
    ..studies indicate that hMRE11 plays a role in MMR, and this function of hMRE11 is most likely mediated by the hMLH1-hMRE11 interaction...
  54. Alemayehu A, Sebova K, Fridrichova I. Redundant DNA methylation in colorectal cancers of Lynch-syndrome patients. Genes Chromosomes Cancer. 2008;47:906-14 pubmed publisher
    ..The crucial cause is DNA mismatch repair (MMR) malfunction that is associated mostly with MLH1 or MSH2 germline mutations...
  55. Wu Q, Vasquez K. Human MLH1 protein participates in genomic damage checkpoint signaling in response to DNA interstrand crosslinks, while MSH2 functions in DNA repair. PLoS Genet. 2008;4:e1000189 pubmed publisher
    ..We hypothesized that MLH1, the common subunit of human MutL complexes, is also involved in the cellular response to psoralen ICLs...
  56. Felsberg J, Thon N, Eigenbrod S, Hentschel B, Sabel M, Westphal M, et al. Promoter methylation and expression of MGMT and the DNA mismatch repair genes MLH1, MSH2, MSH6 and PMS2 in paired primary and recurrent glioblastomas. Int J Cancer. 2011;129:659-70 pubmed publisher
    ..with changes in the promoter methylation status and the expression of MGMT and the DNA mismatch repair (MMR) genes MLH1, MSH2, MSH6 and PMS2 in pairs of primary and recurrent glioblastomas of 80 patients, including 64 patients treated ..
  57. Pinheiro M, Pinto C, Peixoto A, Veiga I, Mesquita B, Henrique R, et al. A novel exonic rearrangement affecting MLH1 and the contiguous LRRFIP2 is a founder mutation in Portuguese Lynch syndrome families. Genet Med. 2011;13:895-902 pubmed publisher
    ..and mutation age determination were performed in 14 unrelated patients and 95 family members presenting the same MLH1 exonic rearrangement, among a series of 84 Lynch syndrome families with germline mutations in MLH1, MSH2, or MSH6...
  58. Kouso H, Yoshino I, Miura N, Takenaka T, Ohba T, Yohena T, et al. Expression of mismatch repair proteins, hMLH1/hMSH2, in non-small cell lung cancer tissues and its clinical significance. J Surg Oncol. 2008;98:377-83 pubmed publisher
    b>hMLH1 and hMSH2 have been implicated to be involved in the DNA mismatch repair (MMR) system...
  59. Niessen R, Hofstra R, Westers H, Ligtenberg M, Kooi K, Jager P, et al. Germline hypermethylation of MLH1 and EPCAM deletions are a frequent cause of Lynch syndrome. Genes Chromosomes Cancer. 2009;48:737-44 pubmed publisher
    It was shown that Lynch syndrome can be caused by germline hypermethylation of the MLH1 and MSH2 promoters...
  60. Perera S, Mrkonjic M, Rawson J, Bapat B. Functional effects of the MLH1-93G>A polymorphism on MLH1/EPM2AIP1 promoter activity. Oncol Rep. 2011;25:809-15 pubmed publisher
    ..We previously showed that the MLH1-93G>A promoter polymorphism is strongly associated with MSI tumours, suggesting a modifier role for this ..
  61. Rubio Del Campo A, Salinas Sanchez A, Sanchez Sanchez F, Giménez Bachs J, Donate Moreno M, Pastor Navarro H, et al. Implications of mismatch repair genes hMLH1 and hMSH2 in patients with sporadic renal cell carcinoma. BJU Int. 2008;102:504-9 pubmed publisher
    To analyse the implications of DNA mismatch repair genes hMLH1 and hMSH2 in sporadic renal cell carcinoma (RCC). Specimens of tumour and healthy renal tissue were collected from 89 patients treated for sporadic RCC...
  62. Poynter J, Siegmund K, Weisenberger D, Long T, Thibodeau S, Lindor N, et al. Molecular characterization of MSI-H colorectal cancer by MLHI promoter methylation, immunohistochemistry, and mismatch repair germline mutation screening. Cancer Epidemiol Biomarkers Prev. 2008;17:3208-15 pubmed publisher
    Microsatellite instability (MSI) occurs in 10% to 20% of colorectal cancers (CRC) and has been attributed to both MLH1 promoter hypermethylation and germline mutation in the mismatch repair (MMR) genes...
  63. Harley I, Rosen B, Risch H, Siminovitch K, Beiner M, McLaughlin J, et al. Ovarian cancer risk is associated with a common variant in the promoter sequence of the mismatch repair gene MLH1. Gynecol Oncol. 2008;109:384-7 pubmed publisher
    ..MLH1 gene are associated with a proportion of families with the hereditary non-polyposis colon cancer syndrome (HNPCC). The cardinal features of the syndrome are a predisposition to colon, endometrial and ovarian cancers...
  64. Tournier I, Vezain M, Martins A, Charbonnier F, Baert Desurmont S, Olschwang S, et al. A large fraction of unclassified variants of the mismatch repair genes MLH1 and MSH2 is associated with splicing defects. Hum Mutat. 2008;29:1412-24 pubmed publisher
    ..have been found in the mismatch repair genes MLH1 and MSH2 involved in hereditary nonpolyposis colorectal cancer (HNPCC or Lynch syndrome)...
  65. Christensen L, Madsen B, Wikman F, Wiuf C, Koed K, Tjønneland A, et al. The association between genetic variants in hMLH1 and hMSH2 and the development of sporadic colorectal cancer in the Danish population. BMC Med Genet. 2008;9:52 pubmed publisher
    Mutations in the mismatch repair genes hMLH1 and hMSH2 predispose to hereditary non-polyposis colorectal cancer (HNPCC)...
  66. Guan H, Ji M, Hou P, Liu Z, Wang C, Shan Z, et al. Hypermethylation of the DNA mismatch repair gene hMLH1 and its association with lymph node metastasis and T1799A BRAF mutation in patients with papillary thyroid cancer. Cancer. 2008;113:247-55 pubmed publisher
    ..Among the 38 PTC tumors examined, 3 of 23 DNA repair genes were hypermethylated, including the hMLH1 gene in 8 of 38 samples (21%), the PCNA gene in 5 of 38 samples (13%), and the OGG1 gene in 2 of 38 samples (5%)...
  67. Soni A, Bansal A, Singh L, Mishra A, Majumdar M, Regina T, et al. Gene expression profile and mutational analysis of DNA mismatch repair genes in carcinoma prostate in Indian population. OMICS. 2011;15:319-24 pubmed publisher
    ..Thus, the present study investigated the gene expression profile of six major MMR genes, viz. hMLH1, hMSH2, hPMS1, hPMS2, hMSH3, and hMSH6, and polymorphism in hMLH1 and hMSH2 in Pca in Indian population...
  68. Morak M, Schackert H, Rahner N, Betz B, Ebert M, Walldorf C, et al. Further evidence for heritability of an epimutation in one of 12 cases with MLH1 promoter methylation in blood cells clinically displaying HNPCC. Eur J Hum Genet. 2008;16:804-11 pubmed publisher
    ..tumours with high microsatellite instability (MSI-H) and loss of MMR protein expression are the hallmarks of HNPCC (Lynch syndrome)...
  69. Hinrichsen I, Brieger A, Trojan J, Zeuzem S, Nilbert M, Plotz G. Expression defect size among unclassified MLH1 variants determines pathogenicity in Lynch syndrome diagnosis. Clin Cancer Res. 2013;19:2432-41 pubmed publisher
    Lynch syndrome is caused by a germline mutation in a mismatch repair gene, most commonly the MLH1 gene. However, one third of the identified alterations are missense variants with unclear clinical significance...
  70. Parsons M, Buchanan D, Thompson B, Young J, Spurdle A. Correlation of tumour BRAF mutations and MLH1 methylation with germline mismatch repair (MMR) gene mutation status: a literature review assessing utility of tumour features for MMR variant classification. J Med Genet. 2012;49:151-7 pubmed publisher
    ..instability (MSI) is caused by either germline mismatch repair (MMR) gene mutations, or 'sporadic' somatic tumour MLH1 promoter methylation. MLH1 promoter methylation is reportedly correlated with tumour BRAF V600E mutation status...
  71. Whiffin N, Broderick P, Lubbe S, Pittman A, Penegar S, Chandler I, et al. MLH1-93G > A is a risk factor for MSI colorectal cancer. Carcinogenesis. 2011;32:1157-61 pubmed publisher
    The -93G > A (rs1800734) polymorphism within the core promoter region of the MutL homolog 1 (MLH1) gene has recently been proposed as a low penetrance variant for colorectal cancer (CRC)...
  72. Mrkonjic M, Roslin N, Greenwood C, Raptis S, Pollett A, Laird P, et al. Specific variants in the MLH1 gene region may drive DNA methylation, loss of protein expression, and MSI-H colorectal cancer. PLoS ONE. 2010;5:e13314 pubmed publisher
    We previously identified an association between a mismatch repair gene, MLH1, promoter SNP (rs1800734) and microsatellite unstable (MSI-H) colorectal cancers (CRCs) in two samples...
  73. Hossain M, Vahter M, Concha G, Broberg K. Environmental arsenic exposure and DNA methylation of the tumor suppressor gene p16 and the DNA repair gene MLH1: effect of arsenic metabolism and genotype. Metallomics. 2012;4:1167-75 pubmed publisher
    ..Methylation of CpGs of the tumor suppressor gene p16, the DNA repair gene MLH1, and the repetitive elements LINE1 was measured by PCR pyrosequencing of blood DNA...
  74. Medeiros F, Lindor N, Couch F, Highsmith W. The germline MLH1 K618A variant and susceptibility to Lynch syndrome-associated tumors. J Mol Diagn. 2012;14:264-73 pubmed publisher
    ..b>MLH1 K618A, which results from a 2-bp alteration (AAG?GCG) leading to a substitution of lysine to alanine in codon 618, ..
  75. Smogorzewska A, Desetty R, Saito T, Schlabach M, Lach F, Sowa M, et al. A genetic screen identifies FAN1, a Fanconi anemia-associated nuclease necessary for DNA interstrand crosslink repair. Mol Cell. 2010;39:36-47 pubmed publisher
    ..We propose that FAN1 is a repair nuclease that is recruited to sites of crosslink damage in part through binding the ubiquitinated ID complex through its UBZ domain. ..
  76. Nilbert M, Wikman F, Hansen T, Krarup H, Orntoft T, Nielsen F, et al. Major contribution from recurrent alterations and MSH6 mutations in the Danish Lynch syndrome population. Fam Cancer. 2009;8:75-83 pubmed publisher
    ..number of mismatch-repair (MMR) gene mutations have been identified in hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndrome...
  77. Helal T, Khamis N, El Sharkawy T, Nada O, Radwan N. Immunohistochemical expression of mismatch repair genes (hMSH2 and hMLH1) in hepatocellular carcinoma in Egypt. APMIS. 2010;118:934-40 pubmed publisher
    ..All cases were examined immunohistochemically to demonstrate the protein expression of hMSH2 and hMLH1. Thirty-two (64%) and 35 (70%) of the HCC cases revealed reduced expression of hMSH2 and hMLH1, respectively...