MSH2

Summary

Gene Symbol: MSH2
Description: mutS homolog 2
Alias: COCA1, FCC1, HNPCC, HNPCC1, LCFS2, DNA mismatch repair protein Msh2, hMSH2, mutS homolog 2, colon cancer, nonpolyposis type 1
Species: human
Products:     MSH2

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. Huang M, Kennedy R, Ali A, Moreau L, Meetei A, D Andrea A, et al. Human MutS and FANCM complexes function as redundant DNA damage sensors in the Fanconi Anemia pathway. DNA Repair (Amst). 2011;10:1203-12 pubmed publisher
    ..Here we show that the MutS homologs function in this capacity. A RNAi screen revealed that MSH2 silencing caused defective FA pathway activation, as assessed by damage-induced FANCD2 mono-ubiquitination...
  3. Belvederesi L, Bianchi F, Galizia E, Loretelli C, Bracci R, Catalani R, et al. MSH2 missense mutations and HNPCC syndrome: pathogenicity assessment in a human expression system. Hum Mutat. 2008;29:E296-309 pubmed publisher
    Hereditary Non-Polyposis Colorectal Cancer (HNPCC) is associated with germline mutations in one of several MisMatch Repair (MMR) genes...
  4. Mangold E, Pagenstecher C, Friedl W, Mathiak M, Buettner R, Engel C, et al. Spectrum and frequencies of mutations in MSH2 and MLH1 identified in 1,721 German families suspected of hereditary nonpolyposis colorectal cancer. Int J Cancer. 2005;116:692-702 pubmed
    Mutations in DNA MMR genes, mainly MSH2 and MLH1, account for the majority of HNPCC, an autosomal dominant predisposition to colorectal cancer and other malignancies...
  5. Ghosal G, Leung J, Nair B, Fong K, Chen J. Proliferating cell nuclear antigen (PCNA)-binding protein C1orf124 is a regulator of translesion synthesis. J Biol Chem. 2012;287:34225-33 pubmed publisher
    ..Thus, C1orf124 acts at multiple steps in TLS, stabilizes RAD18 and ubiquitinated PCNA at damage sites, and facilitates the switch from replicative to TLS polymerase to bypass DNA lesion. ..
  6. 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...
  7. Kurzawski G, Suchy J, Lener M, Kłujszo Grabowska E, Kładny J, Safranow K, et al. Germline MSH2 and MLH1 mutational spectrum including large rearrangements in HNPCC families from Poland (update study). Clin Genet. 2006;69:40-7 pubmed
    ..repair genes MSH2 and MLH1 account for a significant proportion of hereditary non-polyposis colorectal cancer (HNPCC) families...
  8. Zlatanou A, Despras E, Braz Petta T, Boubakour Azzouz I, Pouvelle C, Stewart G, et al. The hMsh2-hMsh6 complex acts in concert with monoubiquitinated PCNA and Pol ? in response to oxidative DNA damage in human cells. Mol Cell. 2011;43:649-62 pubmed publisher
    ..excision repair is not required for this modification of PCNA or Pol? recruitment to chromatin, the presence of hMsh2-hMsh6 is indispensable...
  9. Souza L, Fonseca Silva T, Pereira C, Santos E, Lima L, Carvalho H, et al. Immunohistochemical analysis of p53, APE1, hMSH2 and ERCC1 proteins in actinic cheilitis and lip squamous cell carcinoma. Histopathology. 2011;58:352-60 pubmed publisher
    This study has compared the tissue expression of the p53 tumour suppressor protein and DNA repair proteins APE1, hMSH2 and ERCC1 in normal, dysplastic and malignant lip epithelium...

More Information

Publications100

  1. 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
    hMLH1 and hMSH2 have been implicated to be involved in the DNA mismatch repair (MMR) system...
  2. 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...
  3. Kim J, Roh S, Koo K, Ka I, Kim H, Yu C, et al. Genotyping possible polymorphic variants of human mismatch repair genes in healthy Korean individuals and sporadic colorectal cancer patients. Fam Cancer. 2004;3:129-37 pubmed
    ..Of these 27 variants, 4 (hMSH2 gIVS12-6, hMLH1 655, hMLH1 1151, and hMSH2 1168, in descending order) were identified as SNPs occurring in 4...
  4. Larson E, Duquette M, Cummings W, Streiff R, Maizels N. MutSalpha binds to and promotes synapsis of transcriptionally activated immunoglobulin switch regions. Curr Biol. 2005;15:470-4 pubmed
    ..cytidine deaminase, AID, and conserved DNA repair factors, including the mismatch repair heterodimer, MutSalpha (MSH2/MSH6)...
  5. 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
    ..We examined the phenotypic differences between MLH1 and MSH2 gene mutation carriers and whether mutation type (point versus large rearrangement) affected phenotypic expression...
  6. Niessen R, Berends M, Wu Y, Sijmons R, Hollema H, Ligtenberg M, et al. Identification of mismatch repair gene mutations in young patients with colorectal cancer and in patients with multiple tumours associated with hereditary non-polyposis colorectal cancer. Gut. 2006;55:1781-8 pubmed
    ..colorectal cancer (CRC) or those with multiple tumours associated with hereditary non-polyposis colorectal cancer (HNPCC) raise suspicion of the presence of germline DNA mismatch repair (MMR) gene mutations...
  7. 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)...
  8. Chaksangchaichot P, Punyarit P, Petmitr S. Novel hMSH2, hMSH6 and hMLH1 gene mutations and microsatellite instability in sporadic colorectal cancer. J Cancer Res Clin Oncol. 2007;133:65-70 pubmed
    To detect the hMSH2, hMSH6 and hMLH1 DNA mismatch repair gene mutations and microsatellite instability in somatic colorectal cancer...
  9. Shia J, Klimstra D, Nafa K, Offit K, Guillem J, Markowitz A, et al. Value of immunohistochemical detection of DNA mismatch repair proteins in predicting germline mutation in hereditary colorectal neoplasms. Am J Surg Pathol. 2005;29:96-104 pubmed
    ..of persons with mutations in the DNA mismatch repair (MMR) genes in hereditary nonpolyposis colorectal cancer (HNPCC) remains to be defined...
  10. Plotz G, Piiper A, Wormek M, Zeuzem S, Raedle J. Analysis of the human MutLalpha.MutSalpha complex. Biochem Biophys Res Commun. 2006;340:852-9 pubmed
    ..The described conditions likely capture an intermediate of the repair reaction which has bound ATP and ADP in the two nucleotide-binding sites of MutSalpha. ..
  11. Lee S, Guo J, Lim R, Soo R, Koay E, Salto Tellez M, et al. Clinical and molecular characteristics of hereditary non-polyposis colorectal cancer families in Southeast Asia. Clin Genet. 2005;68:137-45 pubmed
    ..Hereditary non-polyposis colorectal cancer (HNPCC), predominantly due to germline MLH1/MSH2 mutations, is the commonest form of hereditary colorectal cancer (CRC), ..
  12. 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
    ..cumulative risks of developing various tumors using a large series of families with mutations of the MLH1, MSH2, and MSH6 genes...
  13. Barnetson R, Cartwright N, van Vliet A, Haq N, Drew K, Farrington S, et al. Classification of ambiguous mutations in DNA mismatch repair genes identified in a population-based study of colorectal cancer. Hum Mutat. 2008;29:367-74 pubmed
    ..Patient samples were screened for germline mutations in MLH1, MSH2, and MSH6...
  14. 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...
  15. Lützen A, de Wind N, Georgijevic D, Nielsen F, Rasmussen L. Functional analysis of HNPCC-related missense mutations in MSH2. Mutat Res. 2008;645:44-55 pubmed publisher
    Hereditary nonpolyposis colorectal cancer (HNPCC) is associated with germline mutations in the human DNA mismatch repair (MMR) genes, most frequently MSH2 and MLH1...
  16. Pedroni M, Roncari B, Maffei S, Losi L, Scarselli A, Di Gregorio C, et al. A mononucleotide markers panel to identify hMLH1/hMSH2 germline mutations. Dis Markers. 2007;23:179-87 pubmed
    ..testing with two mononucleotide markers, such as BAT25 and BAT26, was sufficient to identify patients with hMLH1/hMSH2 germline mutations...
  17. 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...
  18. 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...
  19. Li L, McVety S, Younan R, Liang P, du Sart D, Gordon P, et al. Distinct patterns of germ-line deletions in MLH1 and MSH2: the implication of Alu repetitive element in the genetic etiology of Lynch syndrome (HNPCC). Hum Mutat. 2006;27:388 pubmed
    ..high frequency of germ-line genomic rearrangements in MLH1 and MSH2 has been reported among Lynch Syndrome (HNPCC) patients from different ethnic populations...
  20. Adamson A, Beardsley D, Kim W, Gao Y, Baskaran R, Brown K. Methylator-induced, mismatch repair-dependent G2 arrest is activated through Chk1 and Chk2. Mol Biol Cell. 2005;16:1513-26 pubmed
    ..Finally, both Chk1 and Chk2 interact with the MMR protein MSH2, and this interaction is enhanced after MNNG exposure, supporting the notion that the MMR system functions as a ..
  21. Kruger S, Bier A, Plaschke J, Hohl R, Aust D, Kreuz F, et al. Ten novel MSH2 and MLH1 germline mutations in families with HNPCC. Hum Mutat. 2004;24:351-2 pubmed
    Hereditary nonpolyposis colorectal cancer (HNPCC) is one of the most common hereditary cancer-susceptibility syndromes. Germline mutations in mismatch repair genes are associated with the clinical phenotype of HNPCC...
  22. Casey G, Lindor N, Papadopoulos N, Thibodeau S, Moskow J, Steelman S, et al. Conversion analysis for mutation detection in MLH1 and MSH2 in patients with colorectal cancer. JAMA. 2005;293:799-809 pubmed
    ..of conversion analysis compared with DNA sequencing alone to detect heterogeneous germline mutations in MLH1, MSH2, and MSH6 in colorectal cancer patients...
  23. Martinez Bouzas C, Ojembarrena E, Beristain E, Errasti J, Viguera N, Tejada Minguéz M. High proportion of large genomic rearrangements in hMSH2 in hereditary nonpolyposis colorectal cancer (HNPCC) families of the Basque Country. Cancer Lett. 2007;255:295-9 pubmed
    Hereditary nonpolyposis colorectal cancer (HNPCC), which represents the most common form of inherited colorectal cancer, results from germline alterations of the mismatch repair genes MSH2, MLH1 and MSH6...
  24. 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)...
  25. Geary J, Sasieni P, Houlston R, Izatt L, Eeles R, Payne S, et al. Gene-related cancer spectrum in families with hereditary non-polyposis colorectal cancer (HNPCC). Fam Cancer. 2008;7:163-72 pubmed
    The family histories of 130 individuals with documented hereditary non-polyposis colorectal cancer (HNPCC) (caused by mutations in mismatch-repair (MMR) genes MSH2 (n = 64), MLH1 (n = 62) or MSH6 (n = 4)) were obtained, and incidence of ..
  26. Hernandez Pigeon H, Quillet Mary A, Louat T, Schambourg A, Humbert O, Selves J, et al. hMutS alpha is protected from ubiquitin-proteasome-dependent degradation by atypical protein kinase C zeta phosphorylation. J Mol Biol. 2005;348:63-74 pubmed
    The hMutS alpha (hMSH2-hMSH6) protein heterodimer plays a critical role in the detection of DNA mispairs in the mismatch repair (MMR) process...
  27. Castellvi Bel S, Castells A, Strunk M, Ferrandez A, Piazuelo E, Mila M, et al. Genomic rearrangements in MSH2 and MLH1 are rare mutational events in Spanish patients with hereditary nonpolyposis colorectal cancer. Cancer Lett. 2005;225:93-8 pubmed
    ..Hereditary nonpolyposis colorectal cancer (HNPCC) is the most frequent autosomal dominant predisposition to the development of CRC, accounting for approximately 2...
  28. Hernandez Pigeon H, Laurent G, Humbert O, Salles B, Lautier D. Degadration of mismatch repair hMutSalpha heterodimer by the ubiquitin-proteasome pathway. FEBS Lett. 2004;562:40-4 pubmed
    Mismatch repair plays a critical role in genome stability. This process requires several proteins including hMSH2/hMSH6 (hMutSalpha) heterodimer involved in the first stage of the process, the mispair recognition...
  29. Lang W, Coats J, Majka J, Hura G, Lin Y, Rasnik I, et al. Conformational trapping of mismatch recognition complex MSH2/MSH3 on repair-resistant DNA loops. Proc Natl Acad Sci U S A. 2011;108:E837-44 pubmed publisher
    ..Here we report that the mismatch recognition complex, MSH2/MSH3, discriminates between a repair-competent and a repair-resistant loop by sensing the conformational dynamics ..
  30. Song H, Ramus S, Quaye L, Dicioccio R, Tyrer J, Lomas E, et al. Common variants in mismatch repair genes and risk of invasive ovarian cancer. Carcinogenesis. 2006;27:2235-42 pubmed
    ..Germline mutations in MMR genes are associated with hereditary non-polyposis colorectal cancer (HNPCC)...
  31. Lynch H, Casey M, Snyder C, Bewtra C, Lynch J, Butts M, et al. Hereditary ovarian carcinoma: heterogeneity, molecular genetics, pathology, and management. Mol Oncol. 2009;3:97-137 pubmed publisher
    ..the hereditary breast-ovarian cancer syndrome, and mutations in mismatch repair genes, the most common of which are MSH2 and MLH1, which predispose to Lynch syndrome...
  32. Shin Y, Heo S, Shin J, Hong S, Ku J, Yoo B, et al. Germline mutations in MLH1, MSH2 and MSH6 in Korean hereditary non-polyposis colorectal cancer families. Hum Mutat. 2004;24:351 pubmed
    Hereditary non-polyposis colorectal cancer (HNPCC), the most common hereditary colon cancer syndrome, is a dominant disorder caused by germline defects in mismatch repair (MMR) genes...
  33. Zhao J, Jain A, Iyer R, Modrich P, Vasquez K. Mismatch repair and nucleotide excision repair proteins cooperate in the recognition of DNA interstrand crosslinks. Nucleic Acids Res. 2009;37:4420-9 pubmed publisher
    ..These data suggest that proteins from the MMR and NER pathways interact in the recognition of ICLs, and provide a mechanistic link by which proteins from multiple repair pathways contribute to ICL repair. ..
  34. Charbonnier F, Baert Desurmont S, Liang P, Di Fiore F, Martin C, Frerot S, et al. The 5' region of the MSH2 gene involved in hereditary non-polyposis colorectal cancer contains a high density of recombinogenic sequences. Hum Mutat. 2005;26:255-61 pubmed
    MSH2 rearrangements are involved in approximately 10% of hereditary non-polyposis colorectal cancer (HNPCC) families, and in most of the rearrangements, exon 1 is deleted...
  35. 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
    ..However, repair mechanisms for ICLs in the human genome are not clearly defined. Previously, we have shown that MSH2, the common subunit of the human MutSalpha and MutSbeta mismatch recognition complexes, plays a role in the error-..
  36. 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
    ..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 with ..
  37. Ligtenberg M, Kuiper R, Chan T, Goossens M, Hebeda K, Voorendt M, et al. Heritable somatic methylation and inactivation of MSH2 in families with Lynch syndrome due to deletion of the 3' exons of TACSTD1. Nat Genet. 2009;41:112-7 pubmed publisher
    ..to colorectal and endometrial cancers owing to inactivating germline mutations in mismatch repair genes, including MSH2 (ref. 1)...
  38. Starinsky S, Figer A, Ben Asher E, Geva R, Flex D, Fidder H, et al. Genotype phenotype correlations in Israeli colorectal cancer patients. Int J Cancer. 2005;114:58-73 pubmed
    ..SNPs from within candidate genes: APC, beta-Catenin, K-RAS, DCC, P16, PTEN, RB1, P15, APOE, ERCC2, P53, MTHFR and hMSH2. Genotyping of consecutive, unselected colorectal cancer patients was done mostly by utilizing the MassARRAY ..
  39. Southey M, Jenkins M, Mead L, Whitty J, Trivett M, Tesoriero A, et al. Use of molecular tumor characteristics to prioritize mismatch repair gene testing in early-onset colorectal cancer. J Clin Oncol. 2005;23:6524-32 pubmed
    ..patients: all from families fulfilling the Amsterdam Criteria for hereditary nonpolyposis colorectal cancer (HNPCC); all with tumors that were high MSI, low MSI, or that lacked expression of any MMR protein; and a random sample ..
  40. Iyer R, Pohlhaus T, Chen S, Hura G, Dzantiev L, Beese L, et al. The MutSalpha-proliferating cell nuclear antigen interaction in human DNA mismatch repair. J Biol Chem. 2008;283:13310-9 pubmed publisher
  41. 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...
  42. Barnetson R, Tenesa A, Farrington S, Nicholl I, Cetnarskyj R, Porteous M, et al. Identification and survival of carriers of mutations in DNA mismatch-repair genes in colon cancer. N Engl J Med. 2006;354:2751-63 pubmed
    ..The identification of mutations in germ-line DNA mismatch-repair genes at the time of diagnosis of colorectal cancer is important in the management of the disease...
  43. Mastrocola A, Heinen C. Nuclear reorganization of DNA mismatch repair proteins in response to DNA damage. DNA Repair (Amst). 2010;9:120-33 pubmed publisher
    ..Using synchronized populations of HeLa cells we demonstrated that hMSH2, hMLH1 and PCNA localize to the chromatin during S-phase, and accumulate to a greater extent in cells treated with ..
  44. Stella A, Surdo N, Lastella P, Barana D, Oliani C, Tibiletti M, et al. Germline novel MSH2 deletions and a founder MSH2 deletion associated with anticipation effects in HNPCC. Clin Genet. 2007;71:130-9 pubmed
    Hereditary non-polyposis colorectal cancer (HNPCC) is caused by inactivating mutations of DNA mismatch repair genes. Large genomic rearrangements in these genes have been increasingly recognized as important causes of HNPCC...
  45. 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...
  46. Dherin C, Gueneau E, Francin M, Nunez M, Miron S, Liberti S, et al. Characterization of a highly conserved binding site of Mlh1 required for exonuclease I-dependent mismatch repair. Mol Cell Biol. 2009;29:907-18 pubmed publisher
    ..Given the conservation of Mlh1 and Exo1 interaction, it may readily impact Mlh1-dependent functions such as cancer prevention in higher eukaryotes. ..
  47. 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...
  48. 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 index and ..
  49. Hu F, Li D, Wang Y, Yao X, Zhang W, Liang J, et al. Novel DNA variants and mutation frequencies of hMLH1 and hMSH2 genes in colorectal cancer in the Northeast China population. PLoS ONE. 2013;8:e60233 pubmed publisher
    Research on hMLH1 and hMSH2 mutations tend to focus on Lynch syndrome (LS) and LS-like colorectal cancer (CRC)...
  50. Yang Q, Zhang R, Wang X, Linke S, Sengupta S, Hickson I, et al. The mismatch DNA repair heterodimer, hMSH2/6, regulates BLM helicase. Oncogene. 2004;23:3749-56 pubmed
    ..mismatch repair components have been implicated in DNA homologous recombination repair, the exact function of hMSH2/6 in this pathway is unclear...
  51. Wang X, Yuan Y, Zhang S, Cai S, Huang Y, Jiang Q, et al. Clinical and genetic characteristics of Chinese hereditary nonpolyposis colorectal cancer families. World J Gastroenterol. 2006;12:4074-7 pubmed
    To analyze the clinical characteristics of Chinese hereditary nonpolyposis colorectal cancer (HNPCC) families and to screen the germline mutations of human mismatch repair genes hMLH1 and hMSH2 in the probands...
  52. Papp J, Kovacs M, Olah E. Germline MLH1 and MSH2 mutational spectrum including frequent large genomic aberrations in Hungarian hereditary non-polyposis colorectal cancer families: implications for genetic testing. World J Gastroenterol. 2007;13:2727-32 pubmed
    ..gene mutations and evaluate the clinical characteristics of Hungarian hereditary non-polyposis colorectal cancer (HNPCC) families...
  53. Pagenstecher C, Wehner M, Friedl W, Rahner N, Aretz S, Friedrichs N, et al. Aberrant splicing in MLH1 and MSH2 due to exonic and intronic variants. Hum Genet. 2006;119:9-22 pubmed
    ..outside the highly conserved splicing region are often found in hereditary nonpolyposis colorectal cancer (HNPCC) families...
  54. Goecke T, Schulmann K, Engel C, Holinski Feder E, Pagenstecher C, Schackert H, et al. Genotype-phenotype comparison of German MLH1 and MSH2 mutation carriers clinically affected with Lynch syndrome: a report by the German HNPCC Consortium. J Clin Oncol. 2006;24:4285-92 pubmed
    ..algorithms, we identified 281 of 574 unrelated families with deleterious germline mutations in MLH1 (n = 124) or MSH2 (n = 157). A total of 988 patients with 1,381 cancers were included in this analysis...
  55. Pinto C, Veiga I, Pinheiro M, Mesquita B, Jeronimo C, Sousa O, et al. MSH6 germline mutations in early-onset colorectal cancer patients without family history of the disease. Br J Cancer. 2006;95:752-6 pubmed
    Germline MLH1 and MSH2 mutations are scarce in young colorectal cancer patients with negative family history of the disease...
  56. Fan Y, Liu X, Zhang H, Dai J, Zhang X, Zhu M, et al. Variations in exon 7 of the MSH2 gene and susceptibility to gastrointestinal cancer in a Chinese population. Cancer Genet Cytogenet. 2006;170:121-8 pubmed
    Epidemiologic, structural, and bioinformatic analyses were used to evaluate variants in the MSH2 and MLH1 genes in 187 subjects with suspected hereditary gastrointestinal cancer in China...
  57. Zhou J, Wang D, Song L, Li S, Ding J, Ma G, et al. [Association of IVS10+12G>A polymorphism in hMSH2 gene with colorectal cancer in Chinese]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2010;27:579-83 pubmed publisher
    To investigate the association of the single-nucleotide polymorphism (SNP) IVS10+12 G>A in hMSH2 gene with colorectal cancer in a Chinese population of Jiangsu province...
  58. Lamberti C, Mangold E, Pagenstecher C, Jungck M, Schwering D, Bollmann M, et al. Frequency of hereditary non-polyposis colorectal cancer among unselected patients with colorectal cancer in Germany. Digestion. 2006;74:58-67 pubmed
    Hereditary non-polyposis colorectal cancer (HNPCC) is a major form of familial colorectal cancer (CRC)...
  59. Poplawski T, Zadrozny M, Kolacinska A, Rykala J, Morawiec Z, Blasiak J. Polymorphisms of the DNA mismatch repair gene HMSH2 in breast cancer occurence and progression. Breast Cancer Res Treat. 2005;94:199-204 pubmed
    ..b>hMSH2 is one of the crucial proteins of MMR...
  60. 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...
  61. Liu S, Zhao B, Wang Z, Wan Y, Huang Y. Clinical features and mismatch repair gene mutation screening in Chinese patients with hereditary nonpolyposis colorectal carcinoma. World J Gastroenterol. 2004;10:2647-51 pubmed
    ..It has been associated with germline mutations in five mismatch repair (MMR) genes (hMSH2, hMLH1, hPMS1, hPMS2, and hMSH6/GTBP). The great majority of germline mutations were found in hMSH2 and hMLH1...
  62. Lagerstedt Robinson K, Liu T, Vandrovcova J, Halvarsson B, Clendenning M, Frebourg T, et al. Lynch syndrome (hereditary nonpolyposis colorectal cancer) diagnostics. J Natl Cancer Inst. 2007;99:291-9 pubmed
    ..In particular, patients with Lynch syndrome, hereditary nonpolyposis colorectal cancer (HNPCC), have an increased risk to develop colorectal cancer at an early age...
  63. Dzantiev L, Constantin N, Genschel J, Iyer R, Burgers P, Modrich P. A defined human system that supports bidirectional mismatch-provoked excision. Mol Cell. 2004;15:31-41 pubmed
    ..By contrast, RFC and PCNA have only a limited effect on 5' to 3' excision directed by a 5' strand break. ..
  64. 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...
  65. Owen B, Yang Z, Lai M, Gajec M, Gajek M, Badger J, et al. (CAG)(n)-hairpin DNA binds to Msh2-Msh3 and changes properties of mismatch recognition. Nat Struct Mol Biol. 2005;12:663-70 pubmed
    Cells have evolved sophisticated DNA repair systems to correct damaged DNA. However, the human DNA mismatch repair protein Msh2-Msh3 is involved in the process of trinucleotide (CNG) DNA expansion rather than repair...
  66. Lastella P, Surdo N, Resta N, Guanti G, Stella A. In silico and in vivo splicing analysis of MLH1 and MSH2 missense mutations shows exon- and tissue-specific effects. BMC Genomics. 2006;7:243 pubmed
    ..We analysed 99 hMLH1 and hMSH2 missense mutations with six different algorithms...
  67. Owen B, H Lang W, McMurray C. The nucleotide binding dynamics of human MSH2-MSH3 are lesion dependent. Nat Struct Mol Biol. 2009;16:550-7 pubmed publisher
    Here we report that the human DNA mismatch complex MSH2-MSH3 recognizes small loops by a mechanism different from that of MSH2-MSH6 for single-base mismatches. The subunits MSH2 and MSH3 can bind either ADP or ATP with similar affinities...
  68. Baert Desurmont S, Buisine M, Bessenay E, Frerot S, Lovecchio T, Martin C, et al. Partial duplications of the MSH2 and MLH1 genes in hereditary nonpolyposis colorectal cancer. Eur J Hum Genet. 2007;15:383-6 pubmed
    ..have highlighted the contribution of MSH2 and MLH1 genomic deletions to hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch's syndrome, but genomic duplications of these genes have been rarely reported...
  69. Gammie A, Erdeniz N, Beaver J, Devlin B, Nanji A, Rose M. Functional characterization of pathogenic human MSH2 missense mutations in Saccharomyces cerevisiae. Genetics. 2007;177:707-21 pubmed
    ..Mutations in either hMSH2 or hMLH1 underlie the majority of HNPCC cases...
  70. Yoshioka K, Yoshioka Y, Hsieh P. ATR kinase activation mediated by MutSalpha and MutLalpha in response to cytotoxic O6-methylguanine adducts. Mol Cell. 2006;22:501-10 pubmed
    ..These results suggest that MMR proteins can act as direct sensors of methylation damage and help recruit ATR-ATRIP to sites of cytotoxic O(6)-meG adducts to initiate ATR checkpoint signaling. ..
  71. Boeckmann L, Schirmer M, Rosenberger A, Struever D, Thoms K, Gutzmer R, et al. Effect of DNA repair host factors on temozolomide or dacarbazine melanoma treatment in Caucasians. Pharmacogenet Genomics. 2009;19:760-9 pubmed publisher
    ..In each patient, the mRNA expression of MGMT and two essential mismatch repair genes, MLH1 and MSH2, was measured in peripheral blood...
  72. 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...
  73. Demokan S, Suoglu Y, Demir D, Gozeler M, Dalay N. Microsatellite instability and methylation of the DNA mismatch repair genes in head and neck cancer. Ann Oncol. 2006;17:995-9 pubmed
    Methylation in the promoter region of the DNA mismatch repair genes hMLH1 and hMSH2 and microsatellite instability at three loci were analyzed in the tumor tissue from patients with head and neck cancer...
  74. 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
    ..cancer and other malignancies, is caused by inactivating mutations of DNA mismatch repair genes, mainly MLH1 and MSH2. Missense mutations affect protein structure or function, but may also cause aberrant splicing, if located within ..
  75. 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 ..
  76. 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...
  77. Ollila S, Dermadi Bebek D, Jiricny J, Nyström M. Mechanisms of pathogenicity in human MSH2 missense mutants. Hum Mutat. 2008;29:1355-63 pubmed publisher
    ..mismatch repair (MMR) gene MSH2 is the second most frequently mutated hereditary nonpolyposis colorectal cancer (HNPCC) susceptibility locus...
  78. Clendenning M, Baze M, Sun S, Walsh K, Liyanarachchi S, Fix D, et al. Origins and prevalence of the American Founder Mutation of MSH2. Cancer Res. 2008;68:2145-53 pubmed publisher
    Large germline deletions within the mismatch repair gene MSH2 account for a significant proportion (up to 20%) of all deleterious mutations of this gene which are associated with Lynch syndrome...
  79. 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...
  80. 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)...
  81. Shahi A, Lee J, Kang Y, Lee S, Hyun J, Chang I, et al. Mismatch-repair protein MSH6 is associated with Ku70 and regulates DNA double-strand break repair. Nucleic Acids Res. 2011;39:2130-43 pubmed publisher
    MSH6, a key component of the MSH2-MSH6 complex, plays a fundamental role in the repair of mismatched DNA bases. Herein, we report that MSH6 is a novel Ku70-interacting protein identified by yeast two-hybrid screening...
  82. Valeri N, Gasparini P, Braconi C, Paone A, Lovat F, Fabbri M, et al. MicroRNA-21 induces resistance to 5-fluorouracil by down-regulating human DNA MutS homolog 2 (hMSH2). Proc Natl Acad Sci U S A. 2010;107:21098-103 pubmed publisher
    ..targets and down-regulates the core mismatch repair (MMR) recognition protein complex, human mutS homolog 2 (hMSH2) and 6 (hMSH6). Colorectal tumors that express a high level of miR-21 display reduced hMSH2 protein expression...
  83. 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...
  84. Baudhuin L, Ferber M, Winters J, Steenblock K, Swanson R, French A, et al. Characterization of hMLH1 and hMSH2 gene dosage alterations in Lynch syndrome patients. Gastroenterology. 2005;129:846-54 pubmed
    ..of Lynch syndrome cases are believed to be due to large genomic alterations in the mismatch repair genes hMLH1 and hMSH2. However, previous studies have not adequately identified the frequency and scope of such mutations, and routine ..
  85. Tian L, Gu L, Li G. Distinct nucleotide binding/hydrolysis properties and molar ratio of MutSalpha and MutSbeta determine their differential mismatch binding activities. J Biol Chem. 2009;284:11557-62 pubmed publisher
    MutSalpha (MSH2/MSH6) and MutSbeta (MSH2/MSH3) are eukaryotic mismatch recognition proteins that preferentially process base-base and small insertion/deletion (ID) mispairs, respectively, despite the fact that cells contain a MutSalpha:..
  86. 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 ..
  87. Domingo E, Laiho P, Ollikainen M, Pinto M, Wang L, French A, et al. BRAF screening as a low-cost effective strategy for simplifying HNPCC genetic testing. J Med Genet. 2004;41:664-8 pubmed
    According to the international criteria for hereditary non-polyposis colorectal cancer (HNPCC) diagnostics, cancer patients with a family history or early onset of colorectal tumours showing high microsatellite instability (MSI-H) should ..
  88. 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...
  89. Park J, Kim D, Hong C, Nam B, Shin Y, Hong S, et al. Germ line mutations of mismatch repair genes in hereditary nonpolyposis colorectal cancer patients with small bowel cancer: International Society for Gastrointestinal Hereditary Tumours Collaborative Study. Clin Cancer Res. 2006;12:3389-93 pubmed
    ..characteristics and mutational profiles of the mismatch repair genes in hereditary nonpolyposis colorectal cancer (HNPCC) patients with small bowel cancer (SBC)...
  90. Watson P, Ashwathnarayan R, Lynch H, Roy H. Tobacco use and increased colorectal cancer risk in patients with hereditary nonpolyposis colorectal cancer (Lynch syndrome). Arch Intern Med. 2004;164:2429-31 pubmed
    ..risk in carriers of HNPCC-associated mutations, using a retrospective cohort study of germline mutation (hMLH1 or hMSH2) carriers from the Hereditary Cancer Institute at Creighton University, one of the oldest and largest registries ..
  91. Tian L, Hou C, Tian K, Holcomb N, Gu L, Li G. Mismatch recognition protein MutSbeta does not hijack (CAG)n hairpin repair in vitro. J Biol Chem. 2009;284:20452-6 pubmed publisher
    ..Evidence presented here provides a novel view as to whether or not MutSbeta is involved in CAG repeat instability in humans. ..