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Mutational signature analysis identifies MUTYH deficiency in colorectal cancers and adrenocortical carcinomas
Author(s) -
Pilati Camilla,
Shinde Jayendra,
Alexandrov Ludmil B,
Assié Guillaume,
André Thierry,
HéliasRodzewicz Zofia,
Ducoudray Romain,
Le Corre Delphine,
ZucmanRossi Jessica,
Emile JeanFrançois,
Bertherat Jérôme,
Letouzé Eric,
LaurentPuig Pierre
Publication year - 2017
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.4880
Subject(s) - mutyh , germline mutation , germline , biology , dna mismatch repair , colorectal cancer , adrenocortical carcinoma , cancer research , lynch syndrome , cancer , microsatellite instability , mutation , genetics , genome instability , gene , dna , dna damage , endocrinology , allele , microsatellite
Abstract Germline alterations in DNA repair genes are implicated in cancer predisposition and can result in characteristic mutational signatures. However, specific mutational signatures associated with base excision repair ( BER ) defects remain to be characterized. Here, by analysing a series of colorectal cancers ( CRCs ) using exome sequencing, we identified a particular spectrum of somatic mutations characterized by an enrichment of C > A transversions in NpCpA or NpCpT contexts in three tumours from a MUTYH ‐associated polyposis ( MAP ) patient and in two cases harbouring pathogenic germline MUTYH mutations. In two series of adrenocortical carcinomas ( ACCs ), we identified four tumours with a similar signature also presenting germline MUTYH mutations. Taken together, these findings demonstrate that MUTYH inactivation results in a particular mutational signature, which may serve as a useful marker of BER ‐related genomic instability in new cancer types. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.