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Online mutation report
Absence of constitutional H2AX gene mutations in 101 hereditary breast cancer families
  1. A N A Monteiro1,
  2. S Zhang2,
  3. C M Phelan2,
  4. S A Narod2
  1. 1Strang Cancer Prevention Center and Department of Cell and Developmental Biology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA
  2. 2Center for Research in Women’s Health, 790 Bay Street, Suite 750A, Toronto M5G1N8, Ontario, Canada
  1. Correspondence to:
 Dr A N A Monteiro, Laboratory of Molecular Oncology, Strang Cancer Research Laboratory, Rockefeller University - Box 231, 1230 York Avenue, New York, NY 10021, USA; 
 monteia{at}rockefeller.edu

https://doi.org/10.1136/jmg.40.4.e51

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    Several genes involved in the DNA damage response and in maintaining genomic stability have emerged as breast cancer susceptibility genes. These include BRCA1 and BRCA2, as well as other genes with smaller contributions to breast cancer aetiology, such as TP53, CHEK2, and ATM. Germline mutations in BRCA1 and BRCA2 increase sensitivity to DNA damage and decrease cellular capacity to repair double strand DNA breaks through homologous recombination.1–3 Interestingly, DNA damage induces activation of ATM (ataxia-telangiectasia mutated), which performs a central role in relaying signals that orchestrate DNA repair.4 People with heterozygous nonsense mutations in ATM appear to display increased susceptibility to breast cancer.5–7 Besides rapidly phosphorylating BRCA1,8 activated ATM also phosphorylates p53 and CHEK2 (CHK2, hCDS1), which have been implicated in breast cancer predisposition. Germline mutations in TP53 or CHEK2 cause Li-Fraumeni syndrome, a multiple cancer phenotype syndrome, which features early onset breast cancer.9,10 Recently, it was found that germline mutations in CHEK2 also increase the relative risk for breast cancer outside the Li-Fraumeni syndrome.11,12 Given …

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