Mutational signature analysis identifies MUTYH deficiency in colorectal cancers and adrenocortical carcinomas
Year: 2017
Type: article
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.
Source: The Journal of Pathology
DOI: 10.1002/path.4880
Institutions: Inserm, Université Paris Descartes, Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique, Université Sorbonne Paris Nord, Sorbonne Paris Cité, Génomique Fonctionnelle des Tumeurs Solides, Université Paris Diderot, Institut Universitaire d'Hématologie, Los Alamos National Laboratory, Centre National de la Recherche Scientifique, Hôpital Cochin, Assistance Publique – Hôpitaux de Paris, Institut Cochin, Hôpital Saint-Antoine, Université Pierre-et-Marie-Curie, Université de Versailles Saint-Quentin-en-Yvelines, Hôpital Ambroise-Paré
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: U.S. Department of Energy, Agence Nationale de la Recherche, Institut National de la Santé et de la Recherche Médicale, Ministère de l'Enseignement Supérieur et de la Recherche, Centre National de la Recherche Scientifique, National Nuclear Security Administration, Los Alamos National Laboratory
OpenAlex ID: W2581568937