Evidence map›Paper›PMID 39974082›Full record

ArticlemedRxiv : the preprint server for health sciences2025

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

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 and 25 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in medRxiv : the preprint server for health sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

35 authors.

Ryan J CorbettCenter for Data-Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.ORCID 0000-0002-3478-0784
Rebecca S KaufmanCenter for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, USA.ORCID 0000-0001-8535-9730
Shelly W McQuaidAnn & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.ORCID 0009-0007-7350-8461
Zalman VaksmanCenter for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, USA.ORCID 0000-0001-5121-8657
Saksham PhulCenter for Data-Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.ORCID 0000-0002-2771-2572
Miguel A BrownCenter for Data-Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.ORCID 0000-0001-6782-1442
Jennifer L MasonCenter for Data-Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.ORCID 0000-0001-5884-2815
Sebastian M WaszakLaboratory of Computational Neuro-Oncology, Swiss Institute for Experimental Cancer Research, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.ORCID 0000-0003-3042-9521
Bo ZhangCenter for Data-Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Chuwei ZhongCenter for Data-Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.ORCID 0000-0003-2406-2735
Emily BlauelCenter for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Heena DesaiDivision of Hematology/Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Ryan HauslerDivision of Hematology/Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Ammar S NaqviCenter for Data-Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.ORCID 0000-0002-0625-666X
Jessica M DaggettCenter for Cancer and Immunology Research, Children's National Hospital, Washington, DC, USA.
Alex SicklerCenter for Cancer and Immunology Research, Children's National Hospital, Washington, DC, USA.
Evan C Cresswell-ClayCenter for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Patricia J SullivanCenter for Cancer and Immunology Research, Children's National Hospital, Washington, DC, USA.
Antonia ChroniCenter for Data-Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.ORCID 0000-0003-3655-8252
Zhuangzhuang GengCenter for Data-Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.ORCID 0009-0007-6883-0691
Elizabeth M GonzalezCenter for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, USA.ORCID 0000-0001-6424-1522
Yuankun ZhuCenter for Data-Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.ORCID 0000-0002-2455-9525
Allison P HeathCenter for Data-Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.ORCID 0000-0002-2583-9668
Marilyn LiDepartment of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.ORCID 0000-0002-4253-2369
Penn Medicine BioBank
Regeneron Genetics Center
Phillip B StormCenter for Data-Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.ORCID 0000-0002-7964-2449
Adam C ResnickCenter for Data-Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.ORCID 0000-0003-0436-4189
Kara N MaxwellDivision of Hematology/Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0001-8192-4202
Kristina A ColeCenter for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, USA.ORCID 0000-0003-0064-2882
Angela J WaandersAnn & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.ORCID 0000-0002-0571-2889
Miriam BornhorstAnn & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.ORCID 0000-0002-7595-7726
Suzanne P MacFarlandCenter for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, USA.ORCID 0000-0001-5894-6403
Jo Lynne RokitaCenter for Data-Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.ORCID 0000-0003-2171-3627
Sharon J DiskinCenter for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, USA.ORCID 0000-0002-7200-8939

Funding

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.U24OD038422 · OD · CHILDREN'S HOSP OF PHILADELPHIA · PI DISKIN, SHARON, GOLDMUNTZ, ELIZABETH · 2024 to 2025
$4.4M
Identification and characterization of genetic risk factors in pediatric brain tumorsR03CA287169 · NCI · CHILDREN'S HOSP OF PHILADELPHIA · PI DISKIN, SHARON, ROKITA, JO LYNNE · 2024 to 2025
$356k
Discovery of neoepitope immunotherapeutic targets in diffuse pediatric high-grade gliomasR03OD036498 · OD · CHILDREN'S HOSP OF PHILADELPHIA · PI ROKITA, JO LYNNE · 2023 to 2023
$356k
Discovering the genetic basis of neuroblastoma initiation and progressionR03CA230366 · NCI · CHILDREN'S HOSP OF PHILADELPHIA · PI DISKIN, SHARON · 2018 to 2019
$344k
NCI NIH HHS R03 CA230366NCI NIH HHS R03 CA287169NIH HHS R03 OD036498NIH HHS U24 OD038422
6 · The paper itself

Abstract

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 23.3% (193/830) of patients and the majority (137/193) lacked clinical reporting of genetic tumor syndromes. Among P/LP carriers, 34.6% 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.

Indexed as

aberrant splicingloss of heterozygositypathogenic germline variantsPediatric brain tumors

Identifiers

PMID39974082
PMCPMC11838646

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.