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Project Achilles pinpoints vulnerabilities in ovarian cancer
Date:7/11/2011

s which of those are important functionally," he said.

The team used a pool of more than 54,000 shRNAs from the library developed by the Broad's RNAi Platform. "The methods that we have developed in the RNAi Platform make it practical and relatively inexpensive to screen shRNAs at a genomic scale and our first area of application was in cancer research," said David Root, director of the RNAi Platform. "The scale-up to the 100 cell lines reported in this most recent paper was a big challenge, but we also saw a huge opportunity. With data on many more cell lines, we would have far, far greater power to identify functionally important cancer targets."

The latest Project Achilles research also addresses a fundamental question in cancer biology. For decades, cancer has been classified based on tissue of origin, but within the last ten years, many scientists have suggested that it may be more revealing to classify tumors based on genetic mutations, regardless of where the cancer first began.

"Many of us in the genomics field including myself were thinking that maybe someday, we won't care about the organs that cancers come from, that we will only care about the genetic mutations that drive them," said Hahn. "What's emerging from TCGA and our Project Achilles work is that lineage will continue to be important."

Hahn suspects that in some cases, this may have to do with the way that different organ systems develop. One of the top genes that the Project Achilles team detected in ovarian cancer cells is PAX8, which plays an important role in the development of the female reproductive system. They found too many copies of PAX8 in 16 percent of the ovarian cancers they examined. In cell lines where PAX8 was overexpressed, suppressing PAX8 led to cell death.

In addition to their findings in ovarian cancer, the researchers found that looking across cancer types can reveal cancer-causing genes, but only if a large number of sample
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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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