Mentor Name: Jo Lynne Rokita

Pathogenic germline variation contributes to cancer risk and clinical outcomes in pediatric central nervous system (CNS) tumors, yet the impact of genetic ancestry on germline variant prevalence and interpretation remains poorly understood. Prior analyses from the Pediatric Brain Tumor Atlas (PBTA) have identified thousands of pathogenic and likely pathogenic germline variants, but existing resources and interpretation frameworks are heavily biased toward individuals of European ancestry. This project will integrate genetic ancestry into germline analyses of pediatric CNS tumors to improve the accuracy and equity of variant interpretation. We will infer genetic ancestry for PBTA participants using both whole genome and whole exome sequencing data and evaluate methods to extend ancestry inference to exome-only samples. We will then characterize ancestry-associated patterns of pathogenic germline variation and assess their relationships with clinical outcomes using established statistical and survival analyses. By enabling ancestry-aware germline analyses across diverse sequencing modalities, this work will enhance the interpretability and clinical relevance of germline findings in pediatric CNS tumors and support more equitable genomic research and precision oncology efforts.