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.

中文翻译：

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儿童癌症的基因组改变格局

检查各种癌症类型之间的共性和差异的泛癌症分析已成为获得癌症生物学新见解的有力方式。在这里，我们对泛癌队列中的基因改变进行了全面分析，该队列包括来自儿童、青少年和年轻成人的 961 种肿瘤，包括 24 种不同的癌症分子类型。使用标准化的工作流程，与之前分析的成人癌症相比，我们发现了突变频率和显着突变基因的显着差异。149 个假定的癌症驱动基因的遗传改变将肿瘤分为两类：小突变和结构/拷贝数变异（与生殖系变异相关）。结构变异、超二倍体和染色体碎裂与 TP53 突变状态和突变特征有关。