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Across 6.5 years, 33% of patients had at least one variant matching a precision oncology trial protocol, and 14% received molecularly targeted therapy, demonstrating translational value from hospital-based sequencing for both research and clinical 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[https://doi.org/10.1038/s41467-024-49944-0](https://doi.org/10.1038/s41467-024-49944-0)  \nMolecular profiling of 888 pediatric tumors informs future precision trials and datasharing initiatives in pediatric cancer  \nReceived: 28 October 2023  \n\n| Accepted: 18 June 2024 |\n| --- |\n| |\n| Check for updates |\n\nSuzanne J. Forrest 1,2 , Hersh Gupta3,4, Abigail Ward1, Yvonne Y. Li 3,4, Duong Doan1, Alyaa Al-Ibraheemi2,5, Sanda Alexandrescu2,5,  \nPratiti Bandopadhayay 1,2, Suzanne Shusterman1,2, Elizabeth A. Mullen 1,2, Natalie B. Collins 1,2, Susan N. Chi1,2, Karen D. Wright1,2, Priti Kumari3, Tali Mazor 3, Keith L. Ligon 2,3,5,6, Priyanka Shivdasani6, Monica Manam5, Laura E. MacConaill6, Evelina Ceca1, Sidney N. Benich1, Wendy B. London 1, Richard L. Schilsky 7, Suanna S. Bruinooge 7, Jaime M. Guidry Auvil8, Ethan Cerami3, Barrett J. Rollins2,3,6, Matthew L. Meyerson 2,3,4,  \nNeal I. Lindeman9, Bruce E. Johnson2,3,6, Andrew D. Cherniack 3,4, Alanna J. Church 2,5 & Katherine A. Janeway 1,2   \nTo inform clinical trial design and real-world precision pediatric oncology practice, we classified diagnoses, assessed the landscape of mutations, and identified genomic variants matching trials in a large unselected institutional cohort of solid tumors patients sequenced at Dana-Farber / Boston Children’s Cancer and Blood Disorders Center. Tumors were sequenced with OncoPanel, a targeted next-generation DNA sequencing panel. Diagnoses were classified according to the International Classification of Diseases for Oncology (ICD-O- 3.2). Over 6.5 years, 888 pediatric cancer patients with 95 distinct diagnoses had successful tumor sequencing. Overall, 33%(n = 289/888) of patients had at least 1 variant matching a precision oncology trial protocol, and 14%(41/289) were treated with molecularly targeted therapy. This study highlights opportunities to use genomic data from hospital-based sequencing performed either for research or clinical care to inform ongoing and future precision oncology clinical trials. Furthermore, the study results emphasize the importance ofdata sharing to define the genomic landscape and targeted treatment opportunities for the large group of rare pediatric cancers we encounter in clinical practice.  \nOver the last 50 years, there has been a profound prolongation in the survival of children and adolescents with cancer, primarily achieved through the intensification of chemotherapy, risk stratification, and multi-modal treatments1,2. Despite these advances, cancer remains the leading cause of death by disease among children in the United States,  \nand many survivors of childhood cancers have significant long-term sequelae from their treatment3–6. Furthermore, progress has not been universal, and a number of specific cancer diagnoses have seen little improvement in outcomes and continue to have a disproportionate burden of treatment-related side effects. Specific groups with lagging  \n1Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, Boston, MA, USA. 2Harvard Medical School, Boston, MA, USA. 3Dana-Farber Cancer Institute, Boston, MA, USA. 4Broad Institute of MIT and Harvard, Cambridge, MA, USA. 5Boston Children’s Hospital, Boston, MA, USA. 6Brigham and Women’s Hospital, Boston, MA, USA. 7American Society of Clinical Oncology, Alexandria, VA, USA. 8National Cancer Institute, Bethesda, MD, USA. 9Weill Cornell Medical College, New York, NY, USA. e-mail: [Suzanne_Forrest@dfci.harvard.edu](Suzanne_Forrest@dfci.harvard.edu); [Katherine_Janeway@dfci.harvard.edu](Katherine_Janeway@dfci.harvard.edu)  \nFig. 1 | CONSORT diagram of analytic cohort. Flow chart illustrating derivation of the final study cohort.  \nimprovement in outcomes include pediatric, adolescent, and young adult (AYA) brain tumors and sarcomas1.  \nOne of the major drivers of improved outcomes and decreased toxicity of therapy is the application of precision oncology, carried out by cancer type-specific characterization of the genome paired with molecularly tar","cbCaimgZgEQ3y8EE","https://ap.wps.com/l/cbCaimgZgEQ3y8EE","pdf",2004056,11,"English","# Results\n## Patient and sample characteristics: sequenced cases have a long tail of ultra-rare diagnoses","[{\"question\":\"How were pediatric tumor diagnoses classified in the study?\",\"answer\":\"Diagnoses were classified according to the International Classification of Diseases for Oncology (ICD-O-3.2).\"},{\"question\":\"What sequencing method and assay were used for tumor profiling?\",\"answer\":\"Tumors were sequenced using OncoPanel, a targeted next-generation DNA sequencing panel.\"},{\"question\":\"What proportion of patients had variants matching precision oncology trial protocols?\",\"answer\":\"Overall, 33% of patients had at least one variant matching a precision oncology trial protocol, and 14% of those were treated with molecularly targeted therapy.\"}]","Molecular profiling of 888 pediatric tumors informs future precision trials and data-sharing initiatives in pediatric cancer | PDF",1790031655,28]