According to the study, Ink4c and Ptch1 genes collaborate to suppress the development of medulloblastoma, the most common pediatric brain tumor. This collaboration between Ink4c and Ptch1 occurs independently of another anticancer collaboration between Ptch1 and the p53 gene, claim the investigators from St Jude Children’s Research Hospital, Rockefeller University, Johns Hopkins University and the University of Newcastle.
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. Based on these findings, the researchers 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.
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.
During the study investigators assessed the specific roles played by Ink4c, Ptch1 and p53 in preventing medulloblastoma using a laboratory model of the human brain tumor. Previous models of medulloblastoma required eliminating the p53 gene, thereby permitting uncontrolled growth of certain nerve cells in the developing cerebellum. However, most human medulloblastoma cases have functional p53 genes.
Instead the team found that models lacking Ptch1 and either one or both Ink4c genes developed medulloblastoma even when p53 function was not subverted. Moreover, the incidence of medulloblastoma was the same regardless of whether one or both copies of Ink4c were missing.