Ink4c And Ptch1 Genes Collaborate To Suppress Medulloblastoma

The Ink4c and Ptch1 genes collaborate to suppress the development of medulloblastoma, the most common pediatric brain tumor, according to investigators at St. Jude Children's Research Hospital, Rockefeller University, Johns Hopkins University and the University of Newcastle (UK). This collaboration between Ink4c and Ptch1 occurs independently of another anti-cancer collaboration: the joint action of Ptch1 with the p53 gene, the researchers said. The discovery sheds new light on how cells in the cerebellum called granule neuronal precursor cells (GNPs) give rise to medulloblastoma when certain genes are absent or not functioning normally. A report on this work appears in the November 15 issue of Genes & Development and is currently available online. Based on these findings, the Pediatric Brain Tumor Program at St. Jude will try to determine if the absence or presence of the Ink4c gene or its protein in medulloblastoma cells can help doctors predict patient outcomes, according to Martine Roussel, Ph.D., a member of the Department of Genetics and Tumor Biology at St. Jude and senior author of the paper. Medulloblastoma arises in the cerebellum, located in the lower, back part of the brain. The cerebellum processes information coming into the brain from the environment to help maintain balance and fine-muscle control. Ptch1 acts like a brake on the activity of a pathway of signals that drives the multiplication of cells; p53 activates a self-destruct mechanism in cells whose DNA is so severely damaged that they might become cancerous. Previously, St. Jude investigators found evidence that Ink4c halts the cycle in which cells repeatedly make new DNA and divide into two daughter cells. By inhibiting this cell division cycle, Ink4c apparently forces GNPs to stop dividing and become specialized and migrate to their final, assigned location deep within the cerebellum. By halting cell division, Ink4c also reduces the chance that mutations arise in the cell's DNA, which is duplicated in each cycle. In a previous study, St. Jude researchers found evidence that inactivation of Ink4c, in combination with other genetic defects, increases the risk of GNPs becoming cancerous and causing medulloblastoma (Cancer Research; 2003 Sept 1; 63 (17):5428-37).

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