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

Clin Genet. 1999 May;55(5):289-304. doi: 10.1034/j.1399-0004.1999.550501.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Ataxia Telangiectasia / diagnosis
  • Ataxia Telangiectasia / genetics*
  • Ataxia Telangiectasia / therapy
  • Ataxia Telangiectasia Mutated Proteins
  • Breast Neoplasms / genetics*
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Female
  • Humans
  • Leukemia / genetics*
  • Male
  • Protein Serine-Threonine Kinases*
  • Proteins / genetics*
  • Tumor Suppressor Proteins


  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Proteins
  • Tumor Suppressor Proteins
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Atm protein, mouse
  • Protein Serine-Threonine Kinases