Abstract IA03: Medulloblastoma predisposition according to molecular subgroup: The usual suspects and beyond

Abstract

Abstract Cancer genomics has illuminated a wide spectrum of genes and core molecular processes contributing to human malignancy. Still, the genetic and molecular basis of many cancers remains only partially explained. Genetic predisposition accounts for 5-10% of cancer diagnoses, and genetic events cooperating with known somatic driver events are poorly understood. Analyzing established cancer predisposition genes in medulloblastoma (MB), a malignant childhood brain tumor, we recently identified pathogenic germline variants that account for 5-6% of all MB patients. The incidence of genetic predisposition to MB varied according to patient age and molecular subgroup status, with up to 25% of childhood SHH-MB patients predicted to harbor pathogenic germline variation. These estimates only account for known cancer predisposition genes, and ongoing studies designed to investigate unknown pathogenic events in the germline of MB patients have implicated novel MB predisposition genes. This presentation aims to summarize these recent insights into genetic predisposition to MB and contextualize these findings with their associated clinical implications. Citation Format: Paul A. Northcott. Medulloblastoma predisposition according to molecular subgroup: The usual suspects and beyond [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr IA03.