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

作者：Pilati Camilla; Shinde Jayendra; Alexandrov Ludmil B; Assie Guillaume; Andre Thierry; Helias Rodzewicz Zofia; Ducoudray Romain; Le Corre Delphine; Zucman Rossi Jessica; Emile Jean Francois; Bertherat Jerome; Letouze Eric; Laurent Puig Pierre^*

来源：Journal of Pathology, 2017, 242(1): 10-15.

DOI：10.1002/path.4880

• mutational signatures
• MUTYH
• colorectal cancer
• adrenocortical carcinomas

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.

• 出版日期2017-5