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Pathway To Breast Cancer

 
  December, 13 2007 10:25
your information resource in human molecular genetics
 
     

Scientists have identified a particular combination of mutations in hereditary breast cancers that typically have a poor prognosis. The pathway identified by the mutations, published online in Nature Genetics, may represent a target for effective therapy.

Women with mutations in the gene BRCA1 are at very high risk of developing basal-like breast cancer, which is one of the subtypes with the worst prognosis. BRCA1 has several roles in the cell, one of which is to promote the repair of damaged DNA. While it is assumed that elevated DNA damage in the absence of normal BRCA1 function must result in additional mutations that promote the development of a tumour, there has been little progress in identifying what these 'downstream' mutations might be.

Based on preliminary work studying mammary cancer in mice, Ramon Parsons and colleagues searched for small chromosomal rearrangements in a known tumour suppressor gene called PTEN in a series of human BRCA1-associated breast cancer cell lines and biopsies. In a significant number of cases they found one or more of these rearrangements in PTEN, resulting in a complete loss of its expression in the tumour cells of both hereditary and non-hereditary breast cancers. This is one of the first specific and recurrent consequences of BRCA1 mutation to be identified in breast cancer, and the authors suggest that drugs targeting the PTEN pathway might be effective in treating this particular subtype. The authors also emphasize the importance of searching for structural rearrangements of this kind in other cancer genomes.

Author contact:

Ramon Parsons (Columbia University Medical Center, New York, NY, USA)
E-mail: rep15@columbia.edu

Abstract available online.

(C) Nature Genetics press release.


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