Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Medline ® Abstract for Reference 96

of 'Molecular genetics of colorectal cancer'

Somatic mutations in MLH1 and MSH2 are a frequent cause of mismatch-repair deficiency in Lynch syndrome-like tumors.
Mensenkamp AR, Vogelaar IP, van Zelst-Stams WA, Goossens M, Ouchene H, Hendriks-Cornelissen SJ, Kwint MP, Hoogerbrugge N, Nagtegaal ID, Ligtenberg MJ
Gastroenterology. 2014;146(3):643. Epub 2013 Dec 10.
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. By using Sanger and ion semiconductor sequencing, 25 MSI-positive tumors were screened for somatic mutations and loss of heterozygosity in mutL homolog 1 (MLH1) and mutS homolog 2 (MSH2). In 13 of 25 tumors (8 MLH1-deficient and 5 MSH2-deficient tumors), 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.
Department of Human Genetics, Radboud university medical center, Nijmegen, The Netherlands. Electronic address: arjen.mensenkamp@radboudumc.nl.