Most common brain cancer may originate in neural ...( ANN ARBOR Mich. University of Mich...),Health

ANN ARBOR, Mich. University of Michigan scientists have found that a deficiency in a key tumor suppressor gene in the brain leads to the most common type of adult brain cancer. The study, conducted in mice that mimic human cancer, points the way to more effective future treatments and a way to screen for the disease early.

Appearing June 2 in Cancer Cell, the U-M team's findings in mice show for the first time that:

• Glioblastoma, the type of cancer that afflicts U.S. Sen. Edward Kennedy and is diagnosed in about 10,000 Americans each year, may originate in neural stem cells located in a brain region known as the subventricular zone, or SVZ.
• In mice, neural stem cells that normally live in this niche give rise to more specialized nerve cells that migrate out of the niche. Cancer could begin with a single genetic mutation in the p53 gene, which makes stem cells migrate out of the niche like their specialized progenies.

Much research on cancer has focused on the p53 gene, known as the "guardian of the genome" because it initiates a wave of other gene actions that normally thwart cancer.

The finding of a specific zone of origin could lead to treatments that may improve the dire median survival rate of 12 months for this type of brain cancer, says Yuan Zhu, Ph.D., the study's senior author and assistant professor in the departments of internal medicine and cell and developmental biology at the U-M Medical School.

"We have to pay more attention to the stem cell niche" in both early detection and treatment, says Zhu. If glioblastoma originates in neural stem cells in the subventricular zone in humans as it does in mice, the study suggests that doctors need to direct treatments there, as well as to the tumor, to eliminate the source of the cancer and keep it from returning, Zhu says.

The findings in mice also may lead in time to effective early screening tests for
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