Germline pathogenic variation impacts somatic alterations and patient outcomes in pediatric central nervous system tumors
Year: 2025
Type: article
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. The role of rare pathogenic/likely pathogenic (P/LP) germline variants in pediatric central nervous system (CNS) tumour development remains poorly understood. Here, the authors investigate the prevalence and clinical significance of germline P/LP variants in cancer predisposition genes across 830 CNS tumour patients.
Source: Nature Communications
Authors: Ryan J. Corbett, Rebecca S. Kaufman, Shelly W. McQuaid, Zalman Vaksman, Saksham Phul, Miguel A. Brown, Jennifer L. Mason, Sebastian M. Waszak, Bo Zhang, Chuwei Zhong, Emily Blauel, Heena Desai, Ryan Hausler, Ammar S. Naqvi, Jessica M. Daggett, Alex Sickler, Evan C. Cresswell-Clay, Patricia J. Sullivan, Antonia Chroni, Zhuangzhuang Geng, Elizabeth M. Gonzalez, Yuankun Zhu, Allison P. Heath, Marilyn Li, Phillip B. Storm, Adam C. Resnick, Kara N. Maxwell, Kristina A. Cole, Angela J. Waanders, Miriam Bornhorst, Suzanne P. MacFarland, Jo Lynne Rokita, Sharon J. Diskin
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Awards: U24-Uncovering the Shared Genetic Origins of Childhood Cancer and Structural Birth Defects Through Enhanced Data Integration and Analysis with the CFDE Data Distillery Knowledge Graph., Discovering the genetic basis of neuroblastoma initiation and progression, G3221630846, G3261351330, G6545640222, Discovery of neoepitope immunotherapeutic targets in diffuse pediatric high-grade gliomas, Identification and characterization of genetic risk factors in pediatric brain tumors, Postdoctoral Training Program in Genomic Medicine
OpenAlex ID: W4416470787