Ataxia-telangiectasia, cancer and the pathobiology of the ATM gene

Author: Meyn, M. Stephen

Source: Clinical Genetics, Volume 55, Number 5, May 1999 , pp. 289-304(16)

Publisher: Blackwell Publishing

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Abstract:

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.

Keywords: apoptosis; ataxia-telangiectasia; ATM; breast cancer; cell cycle checkpoints; leukemia

Document Type: Research article

DOI: 10.1034/j.1399-0004.1999.550501.x

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