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Childhood brain tumor traced to normal stem cells gone bad
Date:8/11/2008

BOSTON--An aggressive childhood brain tumor known as medulloblastoma originates in normal brain "stem" cells that turn malignant when acted on by a known mutant, cancer-causing oncogene, say researchers from Dana-Farber Cancer Institute and the University of California, San Francisco (UCSF).

Reporting in the Aug. 12 issue of Cancer Cell, the scientists say they have uncovered new origins for these tumors from early stem cells as well as more mature cells. Previously, scientists had assumed the tumors might only come from a single source: more mature cells which become neurons and do not have "stem" cell properties. The findings hint at potential new treatment approaches for medulloblastoma by targeting the origins of the tumors, and further suggest that not all patients' tumors may be born from the same cells.

"We now have a better idea of where these brain tumors come from and their relationship to normal stem cells in the brain," said Keith Ligon, MD, PhD, co-senior author of the report and an investigator at the Center for Molecular Oncologic Pathology at Dana-Farber and the Brigham and Women's Hospital in Boston.

Co-senior author, David Rowitch, MD, PhD, currently a professor of pediatrics and neurosurgery at UCSF and a Howard Hughes Medical Institute investigator, commented that mouse experiments shed light on how normal stem cells -- cells with the power to create all types of cells in the brain -- can be transformed into tumors. The transformation occurs when a cell-signaling pathway known as Sonic hedgehog (named for a cartoon character) is reactivated by a chance mutation.

Sonic hedgehog plays an important role during the embryonic development of the brain, but normally shuts down when it's no longer needed. When turned on again by a mutation, the signals can trigger cell processes leading to tumors -- not just in the brain, but in other organs as well.

Medulloblastomas, usually diagnosed in child
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Contact: Bill Schaller
william_schaller@dfci.harvard.edu
617-632-5357
Dana-Farber Cancer Institute
Source:Eurekalert

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