Novel mouse model of medulloblastoma

A collaboration of researchers, led by Dr. Martine Roussel of St. Jude Children's Research Hospital, has developed a novel mouse model of medulloblastoma -- the most prevalent malignant pediatric brain tumor -- that the researchers hope will more accurately represent the genetic changes involved in human brain tumor development.

Their study will be published in the November 15th issue of Genes & Development, but will also be made available online ahead of print on 10/31.

In their upcoming paper, the authors identify a heretofore unknown role for the cyclin-dependent kinase inhibitor, INK4C, in mediating medulloblastoma development, independent of p53 status. Using Ink4c-mutant mice, Dr. Roussel and colleagues demonstrated that Ink4c inactivation cooperates with mutations in Patched (Ptc1, a Shh receptor) to stimulate medulloblastoma formation, even when the p53 gene is intact.

Previously generated highly penetrant models of medulloblastoma rely on p53 loss for tumorigenesis, though in human patients, only about 10% of people actually display p53 mutations. "Preliminary data suggest that INK4c protein expression is diminished in a significant cohort of human medulloblastomas," says Dr. Roussel, "so the Pediatric Brain Tumor Program at our Institution is now planning to include a comprehensive survey of INK4c status in order to determine its prognostic significance."