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

被引:100
作者
Cheadle, Jeremy P. [1 ]
Sampson, Julian. R. [1 ]
机构
[1] Univ Cardiff Wales, Inst Med Genet, Cardiff CF14 4XN, S Glam, Wales
关键词
MUTYH-associated polyposis; MUTYH; MAP; colorectal cancer; base excision repair; MYH;
D O I
10.1016/j.dnarep.2006.11.001
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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. (c) 2006 Elsevier B.V. All rights reserved.
引用
收藏
页码:274 / 279
页数:6
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