Breast cancer gene variants: separating the harmful from the harmless

J Clin Invest. 2009 Oct;119(10):2895-7. doi: 10.1172/JCI40577. Epub 2009 Sep 21.


Individuals carrying a mutation in the breast cancer 1, early onset gene (BRCA1) are at increased risk of breast or ovarian cancer and thus are candidates for risk reduction strategies such as oophorectomy and mastectomy. A recurring problem in the clinic is that many detectable changes within the BRCA1 gene produce subtle alterations to the protein that are not easily recognized as either harmful (loss-of-function) alleles or harmless and thus inconsequential polymorphisms. In this issue of the JCI, Chang, Sharan, and colleagues describe a novel system to evaluate human BRCA1 alleles for in vivo function using BACs containing human BRCA1 vectors in mouse cells and embryos (see the related article beginning on page 3160). This strategy should provide new avenues for clinicians to interpret results of genetic testing of BRCA1 variants and for researchers to study the basic molecular mechanisms of BRCA1 function in in vivo model systems.

Publication types

  • Comment
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / prevention & control
  • Female
  • Genes, BRCA1*
  • Genetic Predisposition to Disease*
  • Genetic Testing
  • Humans
  • Mice
  • Polymorphism, Genetic*