MUTYH encodes a DNA glycosylase involved in oxidative DNA damage repair. The enzyme excises adenine bases from the DNA backbone at sites where adenine is inappropriately paired with guanine, cytosine, or 8-oxo-7,8-dihydroguanine, a major oxidatively damaged DNA lesion. MUTYH functions in a postreplication repair pathway and is targeted to the newly synthesized daughter strand of DNA for removal of the adenine base.
Biallelic MUTYH germline mutations are associated with the autosomal recessive form of intestinal adenomatous polyposis (MUTYH-associated polyposis, or MAP). The most common mutations in Caucasians are the missense substitutions Y165C (494A>G) and G382D (1145G>A). Functional analysis of C165 and D382 proteins has shown a severe decrease of catalytic activity. E466X and Y90X are the common mutations reported in Indian and Pakistani cases. Several other missense, nonsense, in-frame, frameshift and splicing mutations have been found in patients with MAP. Defective base excision repair function associated with MUTYH mutations determines an increase in the somatic mutation rate. Tumors from biallelic MUTYH mutation carriers display an excess of somatic G>T mutations in the APC and KRAS genes.
To date, no somatic MUTYH mutation has been described.
References (open access):
Survival of MUTYH-associated polyposis patients with colorectal cancer and matched control colorectal cancer patients. Nielsen M, van Steenbergen LN, Jones N, Vogt S, Vasen HF, Morreau H, Aretz S, Sampson JR, Dekkers OM, Janssen-Heijnen ML, Hes FJ. J Natl Cancer Inst. 2010 Nov 17;102(22):1724-30.