Journal
JOURNAL OF PATHOLOGY
Volume 242, Issue 1, Pages 10-15Publisher
WILEY
DOI: 10.1002/path.4880
Keywords
mutational signatures; MUTYH; colorectal cancer; adrenocortical carcinomas
Funding
- ARC
- ICE (Interpretation of Clinical Exome) project (FUI, MEDICEN, Region Ile de France)
- J Robert Oppenheimer Fellowship at Los Alamos National Laboratory
- Ministere de l'Enseignement Superieur et de la Recherche [INSERM UMR-S1147]
- Universite Paris-Descartes
- Centre National de la Recherche Scientifique (CNRS)
- Institut National de la Sante et de la Recherche Medicale (INSERM)
- Agence Nationale de la Recherche (ANR Nanobiotechnologies) [ANR-10-NANO-0002-09]
- SIRIC CARPEM
- Canceropole [2011-1-LABEL-UP5-2]
- Ligue Nationale contre le Cancer [EL2016.LNCC/VaT, INSERM U1162]
- PHRC COMETE-Tactic [INSERM U1016]
- US Department of Energy National Nuclear Security Administration [DE-AC52-06NA25396]
- National Nuclear Security Administration of the United States Department of Energy
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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 (C) 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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