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Johns Hopkins gene hunters pinpoint new cancer gene target

Scientists at the Johns Hopkins Kimmel Cancer Center and Howard Hughes Medical Institute have found mutations in a gene linked to the progression of colon and other cancers. The research findings, published online in the March 11 issue of Science, may lead to new therapies and diagnostic tests that target this gene.

The gene in which the mutations have been found, called PIK3CA, is part of a family of genes encoding lipid kinases, enzymes that modify fatty molecules and direct cells to grow, change shape and move. Although scientists have been studying the biochemical properties of this family of genes for more than a decade, until now, no study revealed that they were mutated in cancer.

Kinases have been the focus of recent drug development strategies, with some kinase-inhibiting compounds, such as Gleevec and Herceptin, already being used clinically to inhibit tumor growth.

"These findings open the door to developing specific therapies that may prove useful for the treatment of cancers with mutations in PIK3CA," says Victor Velculescu, M.D., Ph.D., assistant professor of oncology and senior author of the research.

In their current experiments, the scientists sequenced the molecular code of the genes in this lipid kinase family and found mistakes in the nucleotides, or DNA building blocks, in one particular gene, called PIK3CA. Each mistake is a result of one nucleotide being switched for another. PIK3CA mutations were found in 32 percent of colon cancer samples (74/234), as well as 27 percent (4/15) of glioblastomas, 25 percent (3/12) of gastric cancers, 8 percent (1/12) breast cancers and 4 percent (1/24) of lung cancers. By studying 76 additional premalignant colon tumors, the scientists found that PIK3CA mutations may occur at or near the time a tumor is about to invade other tissues.

The investigators demonstrated that the mutations increase PIK3CA kinase activity, which can start a cascade of cellular events
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Contact: Vanessa Wasta
wastava@jhmi.edu
410-955-1287
Johns Hopkins Medical Institutions
11-Mar-2004


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