Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Disruption of chromatin folding domains by somatic genomic rearrangements in human cancer

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson’s disease

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Fine-mapping of 150 breast cancer risk regions identifies 191 likely target genes

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Analyses of non-coding somatic drivers in 2,658 cancer whole genomes

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Patterns of somatic structural variation in human cancer genomes

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Clonal hematopoiesis in elderly twins: concordance, discordance and mortality

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Regulation of ETAA1-mediated ATR activation couples DNA replication fidelity and genome stability

    Research output: Contribution to journalJournal articleResearchpeer-review

  • PCAWG-Structural Variation Working Group
View graph of relations

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.

Original languageEnglish
JournalNature Genetics
ISSN1061-4036
DOIs
Publication statusPublished - 5 Feb 2020

ID: 59265647