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Journal of Cancer Research and Clinical Oncology

Published in:

01-01-2007 | Original Paper

Novel hMSH2, hMSH6 and hMLH1 gene mutations and microsatellite instability in sporadic colorectal cancer

Authors: P. Chaksangchaichot, P. Punyarit, S. Petmitr

Published in: Journal of Cancer Research and Clinical Oncology | Issue 1/2007

Abstract

Purpose

To detect the hMSH2, hMSH6 and hMLH1 DNA mismatch repair gene mutations and microsatellite instability in somatic colorectal cancer.

Patients and methods

The mutations of hMSH2, hMSH6, and hMLH1 genes, including microsatellite instability of BAT-26, BAT-40, D2S123, D5S346 and D17S250 were analyzed in 31 patients with colorectal.

Results

The results revealed that eight cases (25.8%) harbored mutations in DNA mismatch repair genes. Of these, five novel mutations including I237V in exon 4 of hMSH2, ins T at codon 1196 in exon 7 of hMSH6, and ins G at codon 154 in exon 6, N158H in exon 6, and del A at codon 257 in exon 9 of hMLH1 were identified. Moreover, several intronic polymorphisms, including c–g transversion at IVS-1 nt211 + 9 of hMSH2, del T in poly T track at IVS-6 nt3559-5, ATCT duplicate in IVS-7 nt 3642 + 35 and t–g transversion at IVS-10 nt4080 + 185 of hMSH6 were demonstrated in these patients. In addition, seven cases (22.5%) exhibited microsatellite instability (MSI).

Conclusion

These results suggested that the inactivation of DNA mismatch repair genes and microsatellite instability may play a minor role in somatic colorectal cancer development.

Boland CR, Thibodeau SN, Hamilton SR, Sidransky D, Eshleman JR, Burt RW, Meltzer SJ, Rodriguez-Bigas MA, Fodde R, Ranzani GN, Srivastava S (1998) National Cancer Institute workshop on microsatellite instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res 58:5248–5257PubMed

Bubb VJ, Curetis LJ, Cunningham C, Dunlop MG, Carothers AD, Morris RG, White S, Bird CC, Wyllie AH (1996) Microsatellite instability and the role of hMSH2 in sporadic colorectal cancer. Oncogene 12:2641–2649PubMed

Eshleman JR, Markowitz SD (1995) Microsatellite instability inherited and sporadic neoplasms. Curr Opin Oncol 7:83–89PubMed

Farrington SM, Lin-Goerke J, Ling J, Wang Y, Burczak JD, Robbins DJ, Dunlop MG (1998) Systematic analysis of hMSH2 and hMLH1 in young colon cancer patients and controls. Am J Hum Genet 63:749–759PubMedCrossRef

Fearon ER, Vogelstein B (1990) A genetic model for colorectal tumorigenesis. Cell 61:759–767PubMedCrossRef

Fedier A, Fink D (2004) Mutations in DNA mismatch repair genes: Implications for DNA damage signaling and drug sensitivity. Int J Oncol 24:1039–1047PubMed

Fishel R, Lescoe MK, Rao MRS, Copeland NG, Jenkins NA, Garber J, Kane M, Kolodner R (1993) The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer. Cell 75:1027–1038PubMedCrossRef

Heinimann K, Scott RJ, Buerstedde J-M, Weber W, Eiebold K, Attenhofer M, Muller H, Dobbie Z (1999) Influence of selection criteria on mutation detection in patients with hereditary nonpolyposis colorectal cancer. Cancer 85:2512–2518PubMedCrossRef

Holinski-Feder E, Muller-Koch Y, Friedl W, Moeslein G, Keller G, Plaschke J, Ballhausen W, Gross M, Baldwin-Jedele K, Jungck M, Mangold E, Vogelsang H, Schackert HK, Lohsea P, Murken J, Meitinger T (2001) DHPLC mutation analysis of the hereditary nonpolyposis colorectal cancer (HNPCC) genes hMLH1 and hMSH2. J Biochem Biophys Methods 47:21–32PubMedCrossRef

Houlston RS (2001) What we could do now: molecular pathology of colorectal cancer. J Clin Pathol 54:206–214CrossRef

Jacob S, Praz F (2002) DNA mismatch repair defects: role in colorectal Carcinogenesis. Biochimie 84:27–47PubMedCrossRef

Jeong S-Y, Shin K-H, Shin J-H, Ku J-L, Shin Y-K, Park S-Y, Kim W-H, Park J-G (2003) Microsatellite instability and mutations in DNA mismatch repair genes in sporadic colorectal cancers. Dis Colon Rectum 46:1069–1077PubMedCrossRef

Josef J, NystrÖm-Lahti M (2000) Mismatch repair defects in cancer. Curr Opin Genet Dev 10:157–161CrossRef

Kámory E, Kolacsek O, Ottó S, Csuka O (2003) hMLH1 and hMSH2 somatic inactivation mechanisms in sporadic colorectal cancer patients. Pathol Oncol Res 9:236–241PubMedCrossRef

Kariola R, Raevaara TE, Lönnqvist KE, Nyström-Lahti M (2002) Functional analysis of MSH6 mutations linked to kindreds with putative hereditary nonpolyposis colorectal cancer syndrome. Hum Mol Genet 11:1303–1310PubMedCrossRef

Lee JS, Petrelli NJ, Rodriguez-Bigas MA (2001) Rectal cancer in hereditary nonpolyposis colorectal cancer. Am J Surg 181:207–210PubMedCrossRef

Lipton LR, Johnson V, Cummings C, Fisher S, Risby P, Efterkhar Sadat AT, Cranston T, Izatt L, Sasieni P, Hodgson SV, Thomas HJW, Tomlinson IPM (2004) Refining the Amsterdam criteria and Bethesda guidelines: Testing algorithms for the prediction of mismatch repair mutation status in the familial cancer clinic. J Clin Oncol 22:4932–4943CrossRef

Liu B, Nicolaides NC, Markowitz S, Willson JKV, Parsons RE, Jen J, Papadopolous N, Peltomäki P, de la Chapelle A, Hamilton SR, Kinzler KW, Vogelstein B (1995) Mismatch repair gene defects in sporadic colorectal cancers with microsatellite instability. Nat Genet 9:48–55PubMedCrossRef

Lucci-Cordisco E, Rovella V, Carrara S, Percesepe A, Pedroni M, Bellacosa A, Caluseriu O, Forasarig M, Anti M, Neri G, Ponz de Leon M, Viel A, Genuardi M (2001) Mutations of the minor mismatch repair gene MSH6 in typical and atypical hereditary nonpolyposis colorectal cancer. Fam Cancer 1:93–99PubMedCrossRef

Martin N, Patel N (2003) Cancer incidence and leading sites. In: Sriplung H, Sontipong S, Martin N, Wiangnon S, Vootripux V, Cheirsilpa A, Kanchanabat C, Khuhaprema T (eds) Cancer in Thailand, vol III, 1995–1997. National Cancer Institute, Thailand, pp 9–18

Miller SA, Dykes DD, Polesky HFA (1988) Simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16:1215PubMed

Mitchell RJ, Farrington SM, Dunlop MG, Campbell H (2002) Mismatch repair genes hMLH1 and hMSH2 and colorectal cancer: a HuGE review. Am J Epidemiol 156:885–902PubMedCrossRef

Moslein G, Tester DJ, Lindor NM, Honchel R, Cunningham JM, French AJ, Halling KC, Schwab M, Goretzki P, Thibodeau SN (1996) Microsatellite instability and mutation analysis of hMSH2 and hMLH1 in patients with sporadic, familial and hereditary nonpolyposis colorectal cancer. Hum Mol Genet 5:1245–1252PubMedCrossRef

Okuda T, Kawakami K, Ishiquro K, Oda M. Omura K, Watanaba G (2005) The profile of hMLH1 methylation and microsatellite instability in colorectal and non-small cell lung cancer. Int J Mol Med 15:85–90PubMed

Papadopoulos N, Nicolaides NC, Wei Y-W, Ruben SM, Carter KC, Rosen CA, Haseltine WA, Fleischmann RD, Fraser CM, Adams MD, Venter JC, Hamilton SR, Petersen GM, Watson P, Lynch HT, Peltomaki P, Mecklin J-P, de la Chapelle A, Kinzler KW, Vogelstein B (1994) Mutation of mutL homology in hereditary colon cancer. Science 263:1625–1629PubMedCrossRef

Peltomäki P (2001) Deficient DNA mismatch repair: a common etiologic factor for colon cancer. Hum Mol Genet 10:735–740PubMedCrossRef

Petmitr S, Nuchfaong S, Chaksangchaichot P, Pongstaporn W, Sutinont P, Limsila T, Punyarit P (2002) Microsatellite alterations in non-small cell lung cancer. J Exp Clin Cancer Res 21:31–35PubMed

Rosai J (1996) Ackerman’s surgical pathology, 8th edn, vol II. Mosby Year Book Inc., USA

Samowitz WS, Slattery ML, Potter JD, Leppert MF (1999) BAT-26 and BAT-40 instability in colorectal adenomas and carcinomas and germline polymorphism. Am J Path 154:1637–1641PubMed

Samowitz WS, Curtin K, Lin HH, Robertson MA, Schaffer D, Nichols M, Gruenthal K, Leppert MF, Slattery ML (2001) The colon cancer burden of genetically defined hereditary nonpolyposis colorectal cancer. Gastroenterology 121:830–838PubMedCrossRef

Sanguansin S, Petmitr S, Punyarit P, Vorasubin V, Weerapradist W, Surarit R (2006) hMSH2 gene alterations associated with recurrence of oral squamous cell carcinoma. J Exp Clin Cancer Res 25:251–257PubMed

Scartozzi M, Bianchi F, Rosati S, Galizia E, Antolini A, Loretelli C, Piga A, Bearzi I, Cellerino R, Porfiri E (2002) Mutation of hMLH1 and hMSH2 in patients with suspected hereditary nonpolyposis colorectal cancer. J Clin Oncol 20:1203–1208PubMedCrossRef

Vasen HFA, Watson P, Mecklin J-P, Lynch HT, the ICG-HNPCC (1999) New clinical creteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch Syndrome) proposed by the international collaborative group on HNPCC. Gastroenterology 116:1453–1456PubMedCrossRef

Verma L, Kan MF, Brassett C, Schmeits J, Evans DGR, Kolodner RD, Maher ER (1999) Mononucleotide microsatellite instability and germline MSH6 mutation analysis in early onset colorectal cancer. J Med Genet 36:678–682PubMed

Weitz J, Koch M, Deblus J, Höhler T, Galle PR, Büchler MW (2005) Colorectal cancer. Lancet 365:153–165PubMedCrossRef

Title: Novel hMSH2, hMSH6 and hMLH1 gene mutations and microsatellite instability in sporadic colorectal cancer
Authors: P. Chaksangchaichot
P. Punyarit
S. Petmitr
Publication date: 01-01-2007
Publisher: Springer-Verlag
Published in: Journal of Cancer Research and Clinical Oncology / Issue 1/2007
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-006-0147-z

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Abstract

Purpose

Patients and methods

Results

Conclusion

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