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Updated: Jan 10, 2026

Author Spotlight: Finding New Therapeutic Targets for Malignant Peripheral Nerve Sheath Tumor Through Genome-Scale shRNA Screens
Published on: August 25, 2023
Germline pathogenic variation impacts somatic alterations and patient outcomes in pediatric central nervous system
Ryan J Corbett1,2,3,4, Rebecca S Kaufman3,5, Shelly W McQuaid6,7
1Center for Data-Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Abstract:
The contribution of rare pathogenic/likely pathogenic (P/LP) germline variants to pediatric central nervous system (CNS) tumor development remains understudied. Here, we characterize the prevalence and biological significance of germline P/LP variants in cancer predisposition genes across 830 CNS tumor patients from the Pediatric Brain Tumor Atlas (PBTA). We identify germline P/LP variants in 23.3% (193/830) of patients and the majority (137/193) lack clinical reporting of genetic tumor syndromes. Among P/LP carriers, 34.6% have putative somatic second hits or loss of function tumor alterations. Finally, we link pathogenic germline variation with somatic events and patient survival to highlight the impact of germline variation on tumorigenesis and patient outcomes.
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