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Breast cancer's many drivers
Date:6/20/2012

ad of the cancer genomics laboratory at the National Institute of Genomic Medicine, known by its Spanish acronym INMEGEN. "That's exactly the point of doing this type of analysis. It gives you the opportunity to find those genes that you never thought would be involved in the breast cancer process."

The scientists studied two kinds of samples. They sequenced the whole exomes - the tiny fraction of the genome that encodes proteins of 103 breast cancer tumors and DNA from normal tissue from patients in Mexico and Vietnam. They also sequenced the entire genomes of 22 breast cancer tumors and matched normal tissue.

Their analysis confirmed the presence of previously known mutations, but it also turned up the unsuspected alterations.

"One of the lessons here is the real diversity of mutations in breast cancer. I think it's clear there are going to be roughly 50 or so different mutated genes in breast cancer," said Matthew Meyerson, co-senior author of the paper, Broad senior associate member, and professor of pathology at Dana-Farber Cancer Institute and Harvard Medical School. "There's a big diversity of driver genes in cancer. We don't understand what all of them are, but larger data sets will enable us to identify them."

The mutations in CBFB and RUNX1 point to the importance of understanding cell differentiation - how cells become specialized and transcription factors that regulate that process of cell differentiation in epithelial tissue, which lines the inner and outer surfaces of the body. Further studies are needed to unravel that relationship, the authors concluded.

For the current study, inspecting the novel fusion gene MAGI1-AKT3 more closely showed not only that the translocation can transform normal cells into cancer cells, but also that the protein produced by the gene is insensitive to certain drugs now in clinical trials, yet sensitive to others.

In general, fusion genes are created within the same
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Contact: Nicole Davis
ndavis@broadinstitute.org
617-714-7152
Broad Institute of MIT and Harvard
Source:Eurekalert

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