Gastroenterology. 2013 Dec 9. pii: S0016-5085(13)01738-1. doi: 10.1053/j.gastro.2013.12.002. [Epub ahead of print]
Somatic mutations in MLH1 and MSH2 are a Frequent Cause of Mismatch-repair Deficiency in Lynch Syndrome-like Tumors.
Mensenkamp AR1, Vogelaar IP2, van Zelst-Stams WA2, Goossens M3, Ouchene H2, Hendriks-Cornelissen SJ3, Kwint MP3, Hoogerbrugge N2, Nagtegaal ID3,Ligtenberg MJ4.
Abstract
Lynch syndrome is caused by germline mutations in the mismatch repair (MMR) genes. Tumors are characterized by microsatellite instability (MSI). However, a considerable number of MSI-positive tumors have no known molecular mechanism of development. Using Sanger and ion semiconductor sequencing, 25 MSI-positive tumors were screened for somatic mutations and loss of heterozygosity in MLH1 and MSH2. In 13/25 tumors (8 MLH1 deficient and 5 MSH2 deficient), we identified 2 somatic mutations in these genes. We conclude that 2 acquired events explain the MMR-deficiency in more than 50% of the MMR-deficient tumors without causal germline mutations or promoter methylation.
Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.
KEYWORDS:
Lynch-like syndrome, colorectal cancer, genetic, mismatch repair deficiency
- PMID:
- 24333619
- [PubMed - as supplied by publisher]
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