The landscape of genomic alterations across childhood cancers

Abstract

Pan-cancer analyses that examine commonalities and differences among various cancer types have emerged as a powerful way to obtain novel insights into cancer biology. Here we present a comprehensive analysis of genetic alterations in a pan-cancer cohort including 961 tumours from children, adolescents, and young adults, comprising 24 distinct molecular types of cancer. Using a standardized workflow, we identified marked differences in terms of mutation frequency and significantly mutated genes in comparison to previously analysed adult cancers. Genetic alterations in 149 putative cancer driver genes separate the tumours into two classes: small mutation and structural/copy-number variant (correlating with germline variants). Structural variants, hyperdiploidy, and chromothripsis are linked to TP53 mutation status and mutational signatures. Our data suggest that 7–8% of the children in this cohort carry an unambiguous predisposing germline variant and that nearly 50% of paediatric neoplasms harbour a potentially druggable event, which is highly relevant for the design of future clinical trials.

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Affiliated Institutions

• University of Würzburg DE
• University Hospital Augsburg DE
• Universität Ulm DE
• University Hospital Ulm DE
• University Hospital Heidelberg DE
• Hopp Children's Cancer Center Heidelberg DE
• University Hospital of Basel CH
• Klinikum Stuttgart DE
• University Hospital Münster DE
• European Molecular Biology Laboratory DE
• University Medical Center Hamburg-Eppendorf DE
• University Medical Center Freiburg DE
• Universität Hamburg DE
• Amsterdam UMC Location University of Amsterdam NL
• Comprehensive Cancer Center Mainfranken DE
• Charité - Universitätsmedizin Berlin DE
• University Hospital Cologne DE
• St. Jude Children's Research Hospital US
• Universitätsklinikum Gießen und Marburg DE
• Technical University of Munich DE
• Rigshospitalet DK
• Freie Universität Berlin DE
• Heinrich Heine University Düsseldorf DE
• Universitätsmedizin Göttingen DE
• Children's Hospital of Philadelphia US
• German Cancer Research Center DE
• Olgahospital DE
• Christian-Albrechts-Universität zu Kiel DE
• Düsseldorf University Hospital DE
• Princess Máxima Center NL
• Klinik und Poliklinik für Kinder- und Jugendmedizin DE
• Institut Gustave Roussy FR
• National Center for Tumor Diseases DE
• University of Basel CH
• Université Paris-Saclay FR
• Heidelberg University DE
• Medizinische Hochschule Hannover DE
• Essen University Hospital DE
• Klinikum rechts der Isar DE

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