MUTYH-associated polyposis--from defect in base excision repair to clinical genetic testing

DNA Repair (Amst). 2007 Mar 1;6(3):274-9. doi: 10.1016/j.dnarep.2006.11.001. Epub 2006 Dec 11.


Established predisposition genes account for only a small proportion of familial colorectal cancer. Recently, it has been shown that germline mutations in MUTYH predispose to MUTYH-associated polyposis (MAP), an autosomal recessive disorder characterised by multiple colorectal adenomas and carcinomas. MUTYH functions as a base excision repair DNA glycosylase that excises adenines misincorporated opposite 8-oxo-7,8-dihydro-2'-deoxyguanosine, one of the most stable products of oxidative DNA damage. It is the failure to correct this mispair that is thought to give rise to the characteristic signature of G:C-->T:A mutations found in MAP-associated tumours. Here, we review the germline mutation spectrum at the MUTYH locus (comprising 30 truncating and 55 missense/inframe insertion/deletion variants) and the molecular mechanism and biochemical defect(s) underlying this disorder. We also discuss the application of molecular genetic analysis of MUTYH in clinical practice.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenoma / diagnosis
  • Adenoma / genetics
  • Carcinoma / diagnosis
  • Carcinoma / genetics
  • Colorectal Neoplasms / diagnosis*
  • Colorectal Neoplasms / genetics*
  • DNA Glycosylases / genetics*
  • DNA Glycosylases / metabolism
  • DNA Repair*
  • Genetic Predisposition to Disease
  • Genetic Testing
  • Germ-Line Mutation
  • Humans
  • Intestinal Polyposis / diagnosis*
  • Intestinal Polyposis / genetics*
  • Mutation, Missense


  • DNA Glycosylases
  • mutY adenine glycosylase