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

J Pathol. 2017 May;242(1):10-15. doi: 10.1002/path.4880. Epub 2017 Mar 29.


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.

Keywords: MUTYH; adrenocortical carcinomas; colorectal cancer; mutational signatures.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex Neoplasms / genetics*
  • Adrenocortical Carcinoma / genetics*
  • Animals
  • Colorectal Neoplasms / genetics*
  • DNA Glycosylases / deficiency
  • DNA Glycosylases / genetics*
  • DNA Mutational Analysis / methods
  • DNA, Neoplasm / genetics
  • Genetic Predisposition to Disease
  • Germ-Line Mutation
  • Humans
  • Mice, Knockout
  • Mutation*
  • Transcriptome / genetics


  • DNA, Neoplasm
  • DNA Glycosylases
  • mutY adenine glycosylase