Format

Send to

Choose Destination
Gastroenterology. 2014 Mar;146(3):643-646.e8. doi: 10.1053/j.gastro.2013.12.002. Epub 2013 Dec 10.

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

Author information

1
Department of Human Genetics, Radboud university medical center, Nijmegen, The Netherlands. Electronic address: arjen.mensenkamp@radboudumc.nl.
2
Department of Human Genetics, Radboud university medical center, Nijmegen, The Netherlands.
3
Department of Pathology, Radboud university medical center, Nijmegen, The Netherlands.
4
Department of Human Genetics, Radboud university medical center, Nijmegen, The Netherlands; Department of Pathology, Radboud university medical center, Nijmegen, The Netherlands.

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. 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.

KEYWORDS:

Colorectal Cancer; Genetic; Lynch-Like Syndrome; Mismatch Repair Deficiency

Comment in

PMID:
24333619
DOI:
10.1053/j.gastro.2013.12.002
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center