Mutational signature analysis identifies MUTYH deficiency in colorectal cancers and adrenocortical carcinomas.

Related Articles

Mutational signature analysis identifies MUTYH deficiency in colorectal cancers and adrenocortical carcinomas.

J Pathol. 2017 Jan 27;:

Authors: Pilati C, Shinde J, Alexandrov LB, Assié G, André T, Hélias-Rodzewicz Z, Doucoudray R, Le Corre D, Zucman-Rossi J, Emile JF, Bertherat J, Letouzé E, Laurent-Puig P

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 (CRC) 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 (ACC), 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.

PMID: 28127763 [PubMed - as supplied by publisher]

http://ift.tt/2jzQDYZ