Mutational signature analysis identifies MUTYH deficiency in colorectal cancers and adrenocortical carcinomas. Issue 1 (29th March 2017)

• Record Type: Journal Article
• Authors: Pilati, Camilla; Shinde, Jayendra; Alexandrov, Ludmil B; Assié, Guillaume; André, Thierry; Hélias‐Rodzewicz, Zofia; Ducoudray, Romain; Le Corre, Delphine; Zucman‐Rossi, Jessica; Emile, Jean‐François; Bertherat, Jérôme; Letouzé, Eric; Laurent‐Puig, Pierre
• Is Part Of: Journal of pathology. Volume 242:Issue 1(2017)
• Page Start: 10
• Page End: 15
• Publication Date: 2017-03-29
• Subjects: mutational signatures -- MUTYH -- colorectal cancer -- adrenocortical carcinomas; Pathology -- Periodicals; 616.07
• DOI: 10.1002/path.4880
• Languages: English
• ISSNs: 0022-3417

Abstract

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.