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

被引：268

作者：

Mensenkamp, Arjen R. ^{[1
]}

Vogelaar, Ingrid P. ^{[1
]}

van Zelst-Stams, Wendy A. G. ^{[1
]}

Goossens, Monique ^{[2
]}

Ouchene, Hicham ^{[1
]}

Hendriks-Cornelissen, Sandra J. B. ^{[2
]}

Kwint, Michael P. ^{[2
]}

Hoogerbrugge, Nicoline ^{[1
]}

Nagtegaal, Iris D. ^{[2
]}

Ligtenberg, Marjolijn J. L. ^{[1
,2
]}

机构：

[1] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6500 HB Nijmegen, Netherlands

[2] Radboud Univ Nijmegen, Med Ctr, Dept Pathol, NL-6500 HB Nijmegen, Netherlands

来源：

GASTROENTEROLOGY | 2014年 / 146卷 / 03期

关键词：

Genetic; Colorectal Cancer; Mismatch Repair Deficiency; Lynch-Like Syndrome; VARIANT CLASSIFICATION; FUNCTIONAL-ANALYSIS; CANCER; GENE; RISK; RNA; RECOMMENDATIONS; BIOINFORMATICS; METHYLATION; AVOIDANCE;

D O I：

10.1053/j.gastro.2013.12.002

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

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.

引用

页码：643 / +

页数：12

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