Somatic structural variation signatures in pediatric brain tumors.
Somatic structural variation signatures in pediatric brain tumors.
复制标题
儿科脑肿瘤的体细胞结构变异特征。
DOI：
10.1101/2023.05.18.23290139
复制
发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Yang,Lixing
中科院分区：
文献类型：
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作者：
Yang,Yang;Yang,Lixing
脑癌是儿童癌症相关死亡的主要原因。体细胞结构变异(SVS)是DNA的大规模改变，在儿童脑肿瘤中仍然知之甚少。在这里，我们从儿童脑肿瘤图谱的744个儿童脑瘤全基因组序列中检测到总共13,199个高置信度体细胞SVS。在不同的肿瘤类型中，体细胞SV的发生在队列中有巨大的差异性。我们分别对聚簇复杂SVS、非聚簇复杂SVS和简单SVS的突变特征进行分解，以推断它们的突变机制。我们发现许多肿瘤类型携带独特的SV签名，这表明不同的分子机制在不同的肿瘤类型中塑造了基因组的不稳定性。儿童脑肿瘤的体细胞SV信号模式与成人肿瘤有很大的不同。几个主要癌症驱动基因上多个SV信号的汇聚暗示了体细胞SVS在疾病进展中的重要作用。
Brain cancer is the leading cause of cancer-related death in children. Somatic structural variations (SVs), large-scale alterations in DNA, remain poorly understood in pediatric brain tumors. Here, we detect a total of 13,199 high-confidence somatic SVs in 744 whole-genome sequences of pediatric brain tumors from the Pediatric Brain Tumor Atlas. The somatic SV occurrences have tremendous diversity among the cohort and across different tumor types. We decompose mutational signatures of clustered complex SVs, non-clustered complex SVs, and simple SVs separately to infer their mutational mechanisms. Our finding of many tumor types carrying unique sets of SV signatures suggests that distinct molecular mechanisms shape genome instability in different tumor types. The patterns of somatic SV signatures in pediatric brain tumors are substantially different from those in adult cancers. The convergence of multiple SV signatures on several major cancer driver genes implies vital roles of somatic SVs in disease progression.