MEMPHIS, Tenn., Nov. 10 /PRNewswire/ -- The Ink4c and Ptch1 genes collaborate to suppress the development of medulloblastoma, the most common pediatric brain tumor, according to a team of 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.
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.
“Interestingly, when p53 is inactivated, both copies of Ink4c must be disrupted, whereas when Ptch1 is lost, loss of one copy of Ink4c is enough to drive tumorigenesis,” Roussel said. “The fact that the loss of just one copy of the Ink4c gene permits medulloblastoma to develop in certain settings shows that gene dosage is important in mediating the protective effect.”
In the team’s study of 23 human medulloblastoma samples, the Ink4c gene was not expressed in four cases; the section of DNA next to it, called the promoter, had been inactivated. Normally, promoters trigger their target genes to produce RNA, the decoded form of the gene that the cell uses to make a specific protein. In another study of medulloblastomas from 73 children, the investigators found that the Ink4c protein was absent in samples from 14 patients (19 percent) even though Ink4c was present and active.
St. Jude Children’s Research Hospital
St. Jude Children’s Research Hospital is internationally recognized for its pioneering work in finding cures and saving children with cancer and other catastrophic diseases. Founded by late entertainer Danny Thomas and based in Memphis, Tenn., St. Jude freely shares its discoveries with scientific and medical communities around the world. No family ever pays for treatments not covered by insurance, and families without insurance are never asked to pay. St. Jude is financially supported by ALSAC, its fund-raising organization. For more information, please visit http://www.stjude.org.
St. Jude Children’s Research Hospital
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