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Broken genomes behind breast cancers
Date:12/23/2009

rearrangement while others showed more than 200. The study provides detailed insights into the ways that the genome in some cancers have broken and also the processes that were used by the cancer cell in gluing the broken bits of genome back together again.

"It looks as though some breast cancers have a defect in the machinery that maintains and repairs DNA and this defect is resulting in large numbers of these abnormalities," says Dr Andy Futreal of the Wellcome Trust Sanger Institute. "At the moment we do not know what the defect is or the abnormal gene underlying it, but we are seeing the result of its malfunction in the hideously untidy state of these genomes. Identifying the underlying mutated cause will be central to working out how some breast cancers develop."

The broad groups of rearrangement were associated with different subtypes of breast cancer: HER2 positive breast cancers those that are responsive to herceptin have similar patterns of disruption. By the same measure, triple-negative breast cancers, which don't respond to treatment with herceptin or hormones, looked similar.

The size of the DNA regions that are deleted, duplicated or removed ranges from a few hundred letters of DNA code to several millions. Most changes were rearrangements within the same chromosome, but there were also a substantial number involving the joining of two different chromosomes.

Dissecting out the complexity and the diversity of the breast cancer genomes is important for understanding how the cancers arise. Importantly, however, the apparent loss of DNA repair systems raises the possibility of new therapeutic opportunities in some breast cancers.

"It appears that in different subtypes of breast cancers, distinct mechanisms of DNA repair are impaired, leading to different types of genomic disorganisation," suggests Dr Jorge Reis-Filho, team leader from the Breakthrough Breast Cancer Research Centre at The Institute of Ca
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Contact: Don Powell
press.officer@sanger.ac.uk
44-122-349-6928
Wellcome Trust Sanger Institute
Source:Eurekalert

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