Ataxia-telangiectasia, cancer and the pathobiology of the ATM gene.
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.
Meyn
M S
MS
Department of Paediatrics, University of Toronto, Genetics and Genomic Biology Program, The Hospital for Sick Children, ON, Canada. meyn@sickkids.on.ca
D000818:Animals; D001260:Ataxia Telangiectasia / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D064007:Ataxia Telangiectasia Mutated Proteins; D001943:Breast Neoplasms / Q000235:genetics*; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D005260:Female; D006801:Humans; D007938:Leukemia / Q000235:genetics*; D008297:Male; D017346:Protein Serine-Threonine Kinases; D011506:Proteins / Q000235:genetics*; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D011506:Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; D017346:Protein Serine-Threonine Kinases