Premium
Ataxia‐telangiectasia, cancer and the pathobiology of the ATM gene
Author(s) -
Meyn M. Stephen
Publication year - 1999
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1034/j.1399-0004.1999.550501.x
Subject(s) - ataxia telangiectasia , biology , cancer research , mutation , genetics , missense mutation , dna repair , gene , germline mutation , neurodegeneration , dna damage , cell cycle , cancer , disease , dna , medicine , pathology
Ataxia‐telangiectasia (A‐T) is a pleiotropic inherited disease characterized by neurodegeneration, cancer, immunodeficiencies, radiation sensitivity, and genetic instability. Although A‐T homozygotes are rare, the A‐T gene may play a role in sporadic breast cancer and leukemia. ATM , the gene responsible for A‐T, is homologous to several cell cycle checkpoint genes from other organisms. ATM is thought to play a crucial role in a signal transduction network that modulates cell cycle checkpoints, genetic recombination, apoptosis, and other cellular responses to DNA damage. New insights into the pathobiology of A‐T have been provided by the creation of Atm −/− mice and by in vitro studies of ATM function. Analyses of ATM mutations in A‐T patients and in sporadic tumors suggest the existence of two classes of ATM mutation: null mutations that lead to A‐T and dominant negative missense mutations that may predispose to cancer in the heterozygous state.