{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T07:55:34Z","timestamp":1787730934441,"version":"build-2784847793"},"reference-count":35,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"9","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precis Oncol"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>Precision oncology trials have generally focused on tumor testing to identify actionable alterations. The National Cancer Institute\u2014Children'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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PATIENTS AND METHODS<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      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\n                      <jats:italic toggle=\"yes\">NF1<\/jats:italic>\n                      (25.0%) and 25\/163\n                      <jats:italic toggle=\"yes\">TP53<\/jats:italic>\n                      (15.3%) to zero of 27\n                      <jats:italic toggle=\"yes\">ALK<\/jats:italic>\n                      and 18\n                      <jats:italic toggle=\"yes\">PTEN<\/jats:italic>\n                      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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/po-25-00742","type":"journal-article","created":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T20:10:53Z","timestamp":1761855053000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":4,"title":["Germline Cancer Predisposition Results From the National Cancer Institute\u2014Children's Oncology Group Pediatric MATCH Trial"],"prefix":"10.1200","clinical-trial-number":[{"clinical-trial-number":"nct03155620","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2017-0245","authenticated-orcid":true,"given":"Sarah","family":"Scollon","sequence":"first","affiliation":[{"name":"Texas Children's 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