ATM and genome maintenance: defining its role in breast cancer susceptibility

J Mammary Gland Biol Neoplasia. 2004 Jul;9(3):247-62. doi: 10.1023/B:JOMG.0000048772.92326.a1.

Abstract

The ATM gene is mutated in ataxia-telangiectasia (A-T), a genetic instability syndrome characterized by increased cancer risk, as well as other features. Recent studies have shown that the ATM protein kinase plays a critical role in maintaining genome integrity by activating a biochemical chain reaction that in turn leads to cell cycle checkpoint activation and repair of DNA damage. ATM targets include well-known tumor suppressor genes such as p53 and BRCA1, both of which play an important role in predisposition to breast cancer. Studies of A-T families have consistently reported an increased risk of breast cancer in women with one mutated ATM gene, but so far an increased frequency of ATM mutations has not been found in women with breast cancer. Some specific missense and protein truncating variants of ATM have been reported to confer increased breast cancer risk, but the magnitude of this risk remains uncertain. A more comprehensive analysis of ATM is needed in large case-control studies, and in multiple-case breast cancer families.

Publication types

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

MeSH terms

  • Ataxia Telangiectasia
  • Ataxia Telangiectasia Mutated Proteins
  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / pharmacology*
  • DNA Damage*
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / pharmacology*
  • Female
  • Genes, cdc
  • Genetic Predisposition to Disease*
  • Humans
  • Leucine Zippers
  • Pedigree
  • Phosphatidylinositol 3-Kinases
  • Protein Serine-Threonine Kinases / genetics*
  • Protein Serine-Threonine Kinases / pharmacology*
  • Tumor Suppressor Proteins / genetics*
  • Tumor Suppressor Proteins / pharmacology*

Substances

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