Genetic Mutations Linked to Deadly Cancers

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"We found that a typical GBM contains approximately 60 genetic alterations," Velculescu said during the teleconference. "Some of these changes affected many of the same pathways as those in pancreatic cancer. But many were new and appeared to affect the processes that appear to relate to the development of GBM."

One of the important discoveries about GBM was that about 12 percent of patients have an alteration in one gene -- called IDH1 -- that had never before been implicated in any type of cancer. Patients with this particular gene alteration tended to be younger and survive longer, Velculescu said.

"GBMs used to be thought of as one disease. It is now clear that they are two," Velculescu said.

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In another paper on genetic alterations involving GBM tumors, researchers also reported finding alterations that appear to be responsible for the brain cancer.

Dr. Matthew Meyerson, of the Dana-Farber Cancer Institute and Harvard Medical School, and colleagues found three major gene mutations in glioblastoma, namely NF1 (a tumor suppressor gene), ERBB2 (a protein tyrosine kinase gene), and PIK3R1 (a lipid kinase gene) among 206 GBM patients.

"These findings will guide glioblastoma therapies," Meyerson said. "Cancer genome projects can discover important new cancer-causing alterations, with clinical implications. We are on our way to understanding what causes cancer in detail," he said.

Meyerson's findings were published in the Sept. 4 online issue of the journal Nature.

The findings from all three studies could have important treatment and diagnostic implications, Dr. Bert Vogelstein, the Clayton Professor of Oncology and Pathology at Johns Hopkins University and a co-author of the Science paper on GBM, said during a teleconference.

The findings suggest that most solid tumors, particularly those of the brain and pancreas, won't respond to treatments that target a single gene, Vogelstein said. "Our work suggests that it may be more productive to screen for drugs that act against the core pathways that are disregulated in most cancers," he said.

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