Gastroenterology

Gastroenterology

Volume 146, Issue 3, March 2014, Pages 643-646.e8
Gastroenterology

Original Research
Brief Report
Somatic Mutations in MLH1 and MSH2 Are a Frequent Cause of Mismatch-Repair Deficiency in Lynch Syndrome-Like Tumors

https://doi.org/10.1053/j.gastro.2013.12.002Get rights and content

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.

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Acknowledgments

The authors would like to thank Dr Peggy Manders for help with the statistical analyses, and Michiel Oorsprong for excellent technical assistance.

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Conflicts of interest The authors disclose no conflicts.

Funding This work was funded in part by the Radboud University Centre for Oncology, granted in 2010.

Author names in bold designate shared co-first authorship.

Authors share co-first authorship.

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