Microsatellite instability is frequently seen in tumors from patients with hereditary nonpolyposis colorectal cancer (HNPCC). Germline mutations in the mismatch repair gene hMSH2 account for approximately 50% of these cases. Tumors from sporadic cases also exhibit this microsatellite instability phenotype, although at a lower frequency, and very few somatically derived mutations have so far been reported in such tumors. In this study DNA from 23 primary colorectal carcinomas (four familial and 19 sporadic cases) exhibiting microsatellite instability were screened for mutations in the hMSH2 gene using constant denaturant gel electrophoresis (CDGE). Among the sporadic cases, five (26%) were found to have somatically derived mutations. One tumor revealed two different mutations, possibly leading to a homozygous inactivation of the gene. One of the four familial cases was classified as having HNPCC, and a germline as well as a somatic mutation were found in this tumor. These results demonstrate that a considerable proportion of sporadic colorectal cancers with microsatellite instability, have somatic mutations in the hMSH2 gene.
Get the Facts: http://genefacts.org Lynch syndrome is a cancer predisposition syndrome caused by inherited mutations in genes responsible for correcting DNA replication errors. Individuals with Lynch syndrome have a greatly increased risk for colorectal, endometrial, and stomach cancers, and a moderately increased risk for other cancers. Key Points 1-3% of colon cancers attributable to Lynch syndrome Dominant inheritance with reduced penetrance (not all patients with mutations will manifest disease) Diagnosis based on clinical and family history, tumor pathology and/or genetic testing Screening and prophylactic surgeries effective in reducing some, but not all cancer risks Mutations in any of several genes can cause the syndrome
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