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

作者：Sarah Scollon, Sharon E. Plon, Steven Joffe, Jaclyn A. Biegel, Shashikant Kulkarni, George Miles, David R. Patton, Brent Coffey, Cynthia Winter, Gregory J. Tsongalis, Mark J. Routbort, Nilsa C. Ramirez, Lauren Saguilig, Jin Piao, Todd A. Alonzo, Stacey L. Berg, Elizabeth Fox, Brenda J. Weigel, Douglas S. Hawkins, Jeffrey S. Abrams, Margaret Mooney, Naoko Takebe, James V. Tricoli, Katherine A. Janeway, Nita L. Seibel, D. Williams Parsons, Steven Joffe, Sharon E. Plon, Jacquelyn Biegel, Sarah Scollon, Lisa Diller, Conrad V. Fernandez, Swapnil Kulkarni, David Malkin, George Miles, Jennifer A. Oberg, D. Williams Parsons, Mary V. Relling, J. D. Schiffman, Lisa Schwartz, Douglas R. Stewart, James V. Tricoli · 发表于：JCO Precision Oncology · 年份：2025 · DOI：10.1200/po-25-00742 · 被引用次数：3 · 研究领域：Neuroblastoma Research and Treatments、Childhood Cancer Survivors' Quality of Life、Acute Lymphoblastic Leukemia research

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 (...