Pan-cancer analysis of whole genomes reveals driver rearrangements promoted by LINE-1 retrotransposition in human tumours
Eva G. Alvarez,
Young Seok Ju,
Alicia L. Bruzos,
Stefan C. Dentro,
Miguel G. Blanco,
Nicola D Roberts,
Paul A. W. Edwards,
Eunjung Alice Lee,
Jeremiah A. Wala,
Sebastian M. Waszak,
Fabio C. P. Navarro,
Steven E. Schumacher,
Peter J Park,
Jan O. Korbel,
Rebecca C. Fitzgerald,
Peter Van Loo,
Haig H. Kazazian,
Kathleen H. Burns,
Peter J. Campbell,
Jose M. C. Tubio,
on behalf of the PCAWG Structural Variation Working Group,
the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Network
Posted 24 Aug 2017
bioRxiv DOI: 10.1101/179705
Posted 24 Aug 2017
About half of all cancers have somatic integrations of retrotransposons. To characterize their role in oncogenesis, we analyzed the patterns and mechanisms of somatic retrotransposition in 2,954 cancer genomes from 37 histological cancer subtypes. We identified 19,166 somatically acquired retrotransposition events, affecting 35% of samples, and spanning a range of event types. L1 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, sometimes removing tumour suppressor genes, as well as inducing 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 remodelling the cancer genome, with potential implications in the development of human tumours.
- Downloaded 3,444 times
- Download rankings, all-time:
- Site-wide: 1,685 out of 101,401
- In genomics: 338 out of 6,281
- Year to date:
- Site-wide: 7,628 out of 101,401
- Since beginning of last month:
- Site-wide: 15,311 out of 101,401
Downloads over time
Distribution of downloads per paper, site-wide
- 20 Oct 2020: Support for sorting preprints using Twitter activity has been removed, at least temporarily, until a new source of social media activity data becomes available.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!