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.
Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / genetics*
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Adolescent
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Adult
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Aged
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Brain Neoplasms / epidemiology
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Brain Neoplasms / genetics*
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Cohort Studies
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Colorectal Neoplasms / epidemiology
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Colorectal Neoplasms / genetics*
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Colorectal Neoplasms, Hereditary Nonpolyposis / epidemiology
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Colorectal Neoplasms, Hereditary Nonpolyposis / genetics*
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Comorbidity
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DNA Methylation / genetics
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DNA Mismatch Repair / genetics
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Germ-Line Mutation / genetics*
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Humans
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Microsatellite Instability
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Middle Aged
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MutL Protein Homolog 1
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MutS Homolog 2 Protein / genetics*
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Neoplastic Syndromes, Hereditary / epidemiology
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Neoplastic Syndromes, Hereditary / genetics*
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Nuclear Proteins / genetics*
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Promoter Regions, Genetic / genetics
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Retrospective Studies
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Young Adult
Substances
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Adaptor Proteins, Signal Transducing
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MLH1 protein, human
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Nuclear Proteins
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MSH2 protein, human
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MutL Protein Homolog 1
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MutS Homolog 2 Protein