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.
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.
Lynch-like syndrome, colorectal cancer, genetic, mismatch repair deficiency
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