Somatic mutations in MLH1 and MSH2 are a frequent cause of mismatch-repair deficiency in Lynch syndrome-like tumors.

Autor:	Mensenkamp AR; Department of Human Genetics, Radboud university medical center, Nijmegen, The Netherlands. Electronic address: arjen.mensenkamp@radboudumc.nl., Vogelaar IP; Department of Human Genetics, Radboud university medical center, Nijmegen, The Netherlands., van Zelst-Stams WA; Department of Human Genetics, Radboud university medical center, Nijmegen, The Netherlands., Goossens M; Department of Pathology, Radboud university medical center, Nijmegen, The Netherlands., Ouchene H; Department of Human Genetics, Radboud university medical center, Nijmegen, The Netherlands., Hendriks-Cornelissen SJ; Department of Pathology, Radboud university medical center, Nijmegen, The Netherlands., Kwint MP; Department of Pathology, Radboud university medical center, Nijmegen, The Netherlands., Hoogerbrugge N; Department of Human Genetics, Radboud university medical center, Nijmegen, The Netherlands., Nagtegaal ID; Department of Pathology, Radboud university medical center, Nijmegen, The Netherlands., Ligtenberg MJ; Department of Human Genetics, Radboud university medical center, Nijmegen, The Netherlands; Department of Pathology, Radboud university medical center, Nijmegen, The Netherlands.
Jazyk:	angličtina
Zdroj:	Gastroenterology [Gastroenterology] 2014 Mar; Vol. 146 (3), pp. 643-646.e8. Date of Electronic Publication: 2013 Dec 10.
DOI:	10.1053/j.gastro.2013.12.002
Abstrakt:	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. (Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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