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Genomic 'firestorms' underlie aggressive breast cancer progression

COLD SPRING HARBOR, N.Y. (Fri., Dec. 1, 2006) -- The first high-resolution analysis of genomic alterations in breast tumors is reported today in the scientific journal Genome Research. In this analysis, scientists from Cold Spring Harbor Laboratory, in collaboration with researchers from Scandinavia, identified three distinct patterns of genomic variation that underlie breast tumor formation, one of which--'firestorms'--may be predictive of aggressive disease progression and short survival.

"'Firestorms' are violent genomic disruptions that lead to destructive forms of breast cancer, even when the rest of the genome is relatively quiet," explains Dr. Jim Hicks, Senior Research Investigator at Cold Spring Harbor Laboratory and lead author on the paper.

Large-scale DNA alterations in cancer cells--rearrangements, deletions, and duplications--may assist in the proliferation and progression of the disease. "A thorough understanding of these changes will allow the design of more rational therapies," says Hicks. "Doctors will be able to recommend an appropriate course of treatment--hormonal therapy or chemotherapy--based on a patient's genomic profile."

Using a high-resolution genomic profiling technique called ROMA (Representational Oligonucleotide Microarray Analysis; see http://www.cshl.edu/public/releases/revealing.html), the scientists tested genomic DNA samples from 243 breast tumor samples acquired from the Karolinska Institute (Sweden) and the Oslo Micrometastasis Study (Norway). The samples were from patients whose clinical history had been documented, which allowed the scientists to associate the genomic profiles with clinical outcomes.

Most strikingly, Hicks and his co-workers found 'firestorms' of genomic amplification--tight chromosomal clusters where DNA segments had undergone multiple rounds of breakage, copying, and rejoining in a c
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Contact: Maria A. Smit
smit@cshl.edu
516-422-4127
Cold Spring Harbor Laboratory
30-Nov-2006


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