Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Oct:9:e2500742.
doi: 10.1200/PO-25-00742. Epub 2025 Oct 30.

Germline Cancer Predisposition Results From the National Cancer Institute-Children's Oncology Group Pediatric MATCH Trial

Sarah Scollon  1 , Sharon E Plon  1   2 , Steven Joffe  3   4 , Jaclyn A Biegel  5   6 , Shashikant Kulkarni  2 , George Miles  2 , David R Patton  7 , Brent Coffey  7 , Cynthia L Winter  7 , Gregory J Tsongalis  8   9 , Mark J Routbort  10 , Nilsa C Ramirez  11 , Lauren Saguilig  12 , Jin Piao  6 , Todd A Alonzo  6 , Stacey L Berg  1 , Elizabeth Fox  13 , Brenda Weigel  14 , Douglas S Hawkins  15 , Jeffrey S Abrams  16 , Margaret Mooney  16 , Naoko Takebe  16 , James V Tricoli  16 , Katherine A Janeway  17 , Nita L Seibel  16 , D Williams Parsons  1   2 ; NCI-COG Pediatric MATCH Germline Reporting Committee
Collaborators, Affiliations

Germline Cancer Predisposition Results From the National Cancer Institute-Children's Oncology Group Pediatric MATCH Trial

Sarah Scollon et al. JCO Precis Oncol. 2025 Oct.

Abstract

Purpose: Precision oncology trials have generally focused on tumor testing to identify actionable alterations. The National Cancer Institute-Children's Oncology Group Pediatric MATCH trial incorporated return of germline results to assess feasibility of reporting in a cooperative group setting and characterize germline cancer predisposition in patients with refractory cancers.

Patients and methods: Tumor and blood DNA from patients 1-21 years of age with treatment-refractory solid tumors, non-Hodgkin lymphomas, or histiocytic disorders underwent cancer gene panel sequencing. Clinical germline reports returned to 151 study sites included pathogenic/likely pathogenic (P/LP) germline variants found in 38 cancer predisposition genes (CPGs). European Society of Medical Oncology (ESMO) recommendations for germline follow-up of tumor variants in CPGs were assessed.

Results: Both tumor and germline reports were completed for 1,167 patients (87.5% of enrolled). A total of 295 tumor reports (25%) included 361 CPG variants of which 70 variants (19.4%) were found in the germline sample. Three additional germline-only CPG variants resulted in 73 (6.3%) of 1,167 germline reports containing variants across 21 CPGs previously associated with pediatric and/or adult cancers. Among frequently mutated CPGs in tumors, concurrent germline findings ranged from 8/32 NF1 (25.0%) and 25/163 TP53 (15.3%) to zero of 27 ALK and 18 PTEN tumor variants. ESMO guidelines recommended clinical follow-up for 110 (30.5%) of 361 tumor CPG variants which included 40 (57.1%) of 70 germline variants.

Conclusion: Coordinated germline and tumor panel testing was feasible and revealed P/LP CPG variants in 6.3% of the Pediatric MATCH cohort. Tumor variant fraction, germline association of CPG with tumor type, and adult-oriented guidelines were not predictive of germline status, emphasizing the need for systematic germline follow-up after tumor genomic testing for pediatric patients.

Trial registration: ClinicalTrials.gov NCT03155620.

PubMed Disclaimer

Associated data