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<p>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.</p>

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Germline pathogenic variation impacts somatic alterations and patient outcomes in pediatric central nervous system tumors

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月21日

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  • 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

摘要

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.