Germline pathogenic variation impacts somatic alterations and patient outcomes in pediatric CNS tumors.

• Tác giả: Miriam Bornhorst, Miguel A Brown, Antonia Chroni, Kristina A Cole, Ryan J Corbett, Heena Desai, Sharon J Diskin, Zhuangzhuang Geng, Elizabeth M Gonzalez, Ryan Hausler, Allison P Heath, Rebecca S Kaufman, Marilyn Li, Suzanne P MacFarland, Jennifer L Mason, Kara N Maxwell, Shelly W McQuaid, Ammar S Naqvi, Saksham Phul, Adam C Resnick, Jo Lynne Rokita, Phillip B Storm, Zalman Vaksman, Angela J Waanders, Sebastian M Waszak, Bo Zhang, Chuwei Zhong, Yuankun Zhu
• Ngôn ngữ: eng
• Ký hiệu phân loại: 629.453 Guidance, homing, navigation
• Thông tin xuất bản: United States : medRxiv : the preprint server for health sciences , 2025
• Bộ sưu tập: NCBI
• ID: 680589
• Chủ đề: 1. Germline; 2. Pathogenic; 3. Variation

Tóm tắt

The contribution of rare pathogenic/likely pathogenic (P/LP) germline variants to pediatric central nervous system (CNS) tumor development remains understudied. Here, we characterized the prevalence and clinical significance of germline P/LP variants in cancer predisposition genes across 830 CNS tumor patients from the Pediatric Brain Tumor Atlas (PBTA). We identified germline P/LP variants in 24.2% (201/830) of patients and the majority (154/201) lacked clinical reporting of genetic tumor syndromes. Among P/LP carriers, 30.7% had putative somatic second hits or loss of function tumor alterations. Finally, we linked pathogenic germline variation with novel somatic events and patient survival to highlight the impact of germline variation on tumorigenesis and patient outcomes.