About half of all cancers have somatic integrations of retrotransposons. Here, to characterize their role in oncogenesis, we analyzed the patterns and mechanisms of somatic retrotransposition in 2,954 cancer genomes from 38 histological cancer subtypes within the framework of the Pan-Cancer Analysis of Whole Genomes (PCAWG) project. We identified 19,166 somatically acquired retrotransposition events, which affected 35% of samples and spanned a range of event types. Long interspersed nuclear element (LINE-1; L1 hereafter) insertions emerged as the first most frequent type of somatic structural variation in esophageal adenocarcinoma, and the second most frequent in head-and-neck and colorectal cancers. Aberrant L1 integrations can delete megabase-scale regions of a chromosome, which sometimes leads to the removal of tumor-suppressor genes, and can induce complex translocations and large-scale duplications. Somatic retrotranspositions can also initiate breakage-fusion-bridge cycles, leading to high-level amplification of oncogenes. These observations illuminate a relevant role of L1 retrotransposition in remodeling the cancer genome, with potential implications for the development of human tumors.

中文翻译：

---

全基因组的泛癌分析确定了由 LINE-1 逆转录转座促进的驱动基因重排。

大约一半的癌症具有反转录转座子的体细胞整合。在这里，为了描述它们在肿瘤发生中的作用，我们在全基因组泛癌分析 (PCAWG) 项目的框架内分析了来自 38 种组织学癌症亚型的 2,954 个癌症基因组中体细胞逆转录转座的模式和机制。我们确定了 19,166 个体细胞获得性逆转录转座事件，这些事件影响了 35% 的样本并涵盖了一系列事件类型。长散在核元件（LINE-1；以下简称 L1）插入成为食管腺癌中第一种最常见的体细胞结构变异类型，在头颈癌和结直肠癌中排名第二。异常的 L1 整合可以删除染色体的兆碱基规模区域，这有时会导致肿瘤抑制基因的去除，并且可以诱导复杂的易位和大规模复制。体细胞逆转录转座还可以启动断裂-融合-桥循环，导致癌基因的高水平扩增。这些观察阐明了 L1 逆转录转座在重塑癌症基因组中的相关作用，对人类肿瘤的发展具有潜在影响。