Hopp-Children's Cancer Center at the NCT Heidelberg (KiTZ), Heidelberg, Germany.
Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Nature. 2018 Mar 15;555(7696):321-327. doi: 10.1038/nature25480. Epub 2018 Feb 28.
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.
泛癌症分析通过研究各种癌症类型之间的共性和差异，已成为深入了解癌症生物学的一种强大方法。在这里，我们对包括来自儿童、青少年和年轻人的 961 个肿瘤在内的泛癌症队列中的遗传改变进行了全面分析，这些肿瘤包含 24 种不同的癌症分子类型。通过标准化的工作流程，与之前分析的成人癌症相比，我们发现突变频率和显著突变基因存在明显差异。149 个潜在致癌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（与种系变异相关）。结构变异、超二倍体和染色体重排与 TP53 突变状态和突变特征相关。我们的数据表明，该队列中的 7-8%的儿童携带明确的易感性种系变异，近 50%的儿科肿瘤存在潜在可治疗的事件，这对未来临床试验的设计具有重要意义。
