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Somatic MMR Gene Mutations as a Cause for MSI ‐ H Sebaceous Neoplasms in Muir–Torre Syndrome‐Like Patients
Author(s) -
Joly MarieOdile,
Attig Valéry,
Saurin JeanChristophe,
Desseigne Françoise,
Leroux Dominique,
MartinDenavit Tanguy,
Giraud Sophie,
BonnetDupeyron MarieNoëlle,
Faivre Laurence,
Auclair Jessie,
GrandMasson Chloé,
Audoynaud Carole,
Wang Qing
Publication year - 2015
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.22740
Subject(s) - microsatellite instability , biology , lynch syndrome , germline mutation , loss of heterozygosity , dna mismatch repair , germline , somatic cell , genetics , sebaceous carcinoma , mutation , gene , cancer research , microsatellite , carcinoma , dna repair , allele
Sebaceous neoplasms are a major clinical feature of M uir– T orre syndrome ( MTS ) associated with visceral malignancies, especially colorectal and endometrial tumors. The diagnosis of MTS relies largely on the microsatellite instability ( MSI ) phenotype in tumors, suggesting germline mutations in DNA mismatch repair ( MMR ) genes responsible for the inherited disease. We hypothesized that in some MSI ‐ H sebaceous tumors, acquired rather than inherited mutations in MMR genes could be involved. Using next‐generation sequencing, we screened MMR gene mutations in 18 MSI ‐ H sebaceous tumors. We found mutations in 17 samples (94%). Indeed, 12/17 (71%) were shown to carry acquired somatic mutations and among 12 samples, seven were shown to be associated with additional somatic alterations like loss of heterozygosity or multiple mutations, suggesting somatic second hits. Our findings strongly suggest that somatic MMR deficiency is responsible for a proportion of MSI ‐ H sebaceous tumors.