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Åke Borg

Åke Borg

Principal investigator

Åke Borg

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 Edwards
  • Joachim Weischenfeldt
  • Montserrat Puiggròs
  • Zechen Chong
  • Ken Chen
  • Eunjung Alice Lee
  • Jeremiah A Wala
  • Keiran M 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
  • Iñigo Martincorena
  • Rebecca C Fitzgerald
  • Peter Van Loo
  • Haig H Kazazian
  • Kathleen H Burns
  • Peter J Campbell
  • Jose M C Tubio
Show all

Other contributions

  • Åke Borg
  • Markus Ringnér
  • Johan Staaf

Summary, in English

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.

Department/s

  • LUCC: Lund University Cancer Centre
  • Familial Breast Cancer
  • Breastcancer-genetics
  • Molecular Cell Biology
  • Breast/lungcancer
  • Division of Translational Cancer Research
  • Research Group Lung Cancer

Publishing year

2020-03

Language

English

Pages

306-319

Publication/Series

Nature Genetics

Volume

52

Issue

3

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Medical Genetics

Keywords

  • Carcinogenesis/genetics
  • Gene Rearrangement/genetics
  • Genome, Human/genetics
  • Humans
  • Long Interspersed Nucleotide Elements/genetics
  • Neoplasms/genetics
  • Retroelements/genetics

Status

Published

Research group

  • Familial Breast Cancer
  • Research Group Lung Cancer

ISBN/ISSN/Other

  • ISSN: 1546-1718