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Hunt for DNA amplified in cancers uncovers important target gene

Boston -- Researchers at Harvard Medical School (HMS) and Massachusetts General Hospital (MGH) have discovered a new cancer-promoting role for a gene potentially involved in breast, liver, and other kinds of cancers. Their discovery that the gene YAP can transform mammary epithelial cells opens the door to understanding how a novel cell growth controlling pathway first discovered in fruit flies might be important in human cancers. This work is published in the Aug. 8 online early edition of the Proceedings of the National Academy of Sciences and will appear in the Aug. 15 print edition.

"We screened the DNA from breast cancer cells for amplifications that are associated with tumor development. The identification of these new potential cancer-causing genes is critical to uncovering novel pathways that drive the conversion of a normal cell to a cancerous one." says senior author Daniel Haber, MD, PhD, the Laurel Schwartz professor of medicine at HMS and MGH and director of the MGH Cancer Center. This research was conducted jointly by Haber's lab and the lab of Joan Brugge, PhD, professor and chair of the Department of Cell Biology at HMS.

Through microarray analysis of a mammary tumor in a BRCA1/p53 deficient mouse model, Haber's group discovered an amplified region of DNA in the mouse breast tumor that contained only one known gene, called YAP.

"A similar region of DNA is also amplified in some human tumors, but this amplified region often contains other genes that are known to promote cell survival," says Haber, who worked with co-authors Jianmin Zhang, PhD, and Gromoslaw Smolen, PhD, both research fellows at MGH. "Thus, whether the YAP gene could play a role in these cancers had been largely ignored. The amplified region we discovered excluded these other genes, which allowed us to focus on YAP as a new candidate."

The YAP gene has an interesting literature associated with it that comes from the fruit fly Drosophila mela
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Contact: Leah Gourley
public_affairs@hms.harvard.edu
617-432-0442
Harvard Medical School
7-Aug-2006


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