英国剑桥惠康桑格研究所Jose M. C. Tubio和西班牙圣地亚哥德孔波斯特拉大学Peter J. Campbell研究组合作，发现全基因组的全癌分析确定了LINE-1逆转座促进了驱动程序重排。这一研究成果2020年2月5日在线发表在国际学术期刊《自然—遗传学》上。
为了表征逆转座在肿瘤发生中的作用，他们在全基因组全癌分析（PCAWG）项目的框架内，分析了来自38种组织学亚型的2,954个癌症基因组中的体细胞逆转座的模式和机制。他们鉴定了19,166个个体，并从中获得逆转座事件，这些事件影响了35％的样本并涵盖了一系列事件类型。长间隔核序列插入（LINE-1；以下称L1）是食管腺癌中最常见的体细胞结构变异类型，而在头颈部和结直肠癌中则是第二常见的体细胞结构变异类型。异常的L1整合可以删除染色体的兆碱基级区域，这有时会导致肿瘤抑制基因的敲除，并且可以诱导复杂的易位和大规模重复。体细胞逆转座也可以启动断裂-融合-桥循环，导致癌基因的高水平扩增。这些结果阐明了L1逆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的影响。
研究人员表示，所有癌症中约有一半具有逆转录转座子的体细胞整合。
附：英文原文
Title: Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition
Author: Bernardo Rodriguez-Martin, Eva G. Alvarez, Adrian Baez-Ortega, Jorge Zamora, Fran Supek, Jonas Demeulemeester, Martin Santamarina, Young Seok Ju, Javier Temes, Daniel Garcia-Souto, Harald Detering, Yilong Li, Jorge Rodriguez-Castro, Ana Dueso-Barroso, Alicia L. Bruzos, Stefan C. Dentro, Miguel G. Blanco, Gianmarco Contino, Daniel Ardeljan, Marta Tojo, Nicola D. Roberts, Sonia Zumalave, Paul A. W. Edwards, Joachim Weischenfeldt, Montserrat Puiggrs, Zechen Chong, Ken Chen, Eunjung Alice Lee, Jeremiah A. Wala, Keiran Raine, Adam Butler, Sebastian M. Waszak, Fabio C. P. Navarro, Steven E. Schumacher, Jean Monlong, Francesco Maura, Niccolo Bolli, Guillaume Bourque, Mark Gerstein, Peter J. Park, David C. Wedge, Rameen Beroukhim, David Torrents, Jan O. Korbel, Inigo Martincorena, Rebecca C. Fitzgerald, Peter Van Loo, Haig H. Kazazian, Kathleen H. Burns, Peter J. Campbell, Jose M. C. Tubio
Issue&Volume: 2020-02-05
Abstract: 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 2,954cancer genomes from 38histological cancer subtypes within the framework of the Pan-Cancer Analysis of Whole Genomes (PCAWG) project. We identified 19,166somatically 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.
DOI: 10.1038/s41588-019-0562-0
Source: https://www.nature.com/articles/s41588-019-0562-0
Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
官方网址：https://www.nature.com/ng/
投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex
本期文章：《自然—遗传学》：Online/在线发表
