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Microsatellite Instability and Mismatch Repair Gene Inactivation in Sporadic Pancreatic and Colon Tumours

Overview
Journal Br J Cancer
Specialty Oncology
Date 1999 Jul 2
PMID 10389971
Citations 17
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Abstract

Genomic instability has been proposed as a new mechanism of carcinogenesis involved in hereditary non-polyposis colorectal cancer (HNPCC) and in a large number of sporadic cancers like pancreatic and colon tumours. Mutations in human mismatch repair genes have been found in HNPCC patients, but their involvement in sporadic cancer has not been clarified yet. In this study we screened 21 pancreatic and 23 colorectal sporadic cancers for microsatellite instability by ten and six different microsatellite markers respectively. Microsatellite alterations were observed at one or more loci in 66.6% (14/21) of pancreatic cancers and in 26% (6/23) colon tumours, but all the pancreatic and half of the colon samples showed a low rate of microsatellite instability. All the unstable samples were further analysed for mutations in the hMLH1 and hMSH2 genes and for hypermethylation of the hMLH1 promoter region. Alterations in the hMLH1 gene were found only in colorectal tumours with a large presence of microsatellite instability. None of the pancreatic tumours showed any alteration in the two genes analysed. Our results demonstrate that microsatellite instability is unlikely to play a role in the tumorigenesis of sporadic pancreatic cancers and confirm the presence of mismatch repair gene alterations only in sporadic colon tumours with a highly unstable phenotype.

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References
1.
Parsons R, Li G, Longley M, Fang W, Papadopoulos N, Jen J . Hypermutability and mismatch repair deficiency in RER+ tumor cells. Cell. 1993; 75(6):1227-36. DOI: 10.1016/0092-8674(93)90331-j. View

2.
Nicolaides N, Littman S, Modrich P, Kinzler K, Vogelstein B . A naturally occurring hPMS2 mutation can confer a dominant negative mutator phenotype. Mol Cell Biol. 1998; 18(3):1635-41. PMC: 108878. DOI: 10.1128/MCB.18.3.1635. View

3.
Fodde R, Losekoot M . Mutation detection by denaturing gradient gel electrophoresis (DGGE). Hum Mutat. 1994; 3(2):83-94. DOI: 10.1002/humu.1380030202. View

4.
Bhattacharyya N, Skandalis A, Ganesh A, Groden J, Meuth M . Mutator phenotypes in human colorectal carcinoma cell lines. Proc Natl Acad Sci U S A. 1994; 91(14):6319-23. PMC: 44193. DOI: 10.1073/pnas.91.14.6319. View

5.
Kim H, Jen J, Vogelstein B, Hamilton S . Clinical and pathological characteristics of sporadic colorectal carcinomas with DNA replication errors in microsatellite sequences. Am J Pathol. 1994; 145(1):148-56. PMC: 1887287. View