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Åke Borg

Åke Borg

Principal investigator

Åke Borg

Patterns of somatic structural variation in human cancer genomes

Author

  • Yilong Li
  • Nicola D Roberts
  • Jeremiah A Wala
  • Ofer Shapira
  • Steven E Schumacher
  • Kiran Kumar
  • Ekta Khurana
  • Sebastian Waszak
  • Jan O Korbel
  • James E Haber
  • Marcin Imielinski
  • Joachim Weischenfeldt
  • Rameen Beroukhim
  • Peter J Campbell
Show all

Other contributions

  • Åke Borg
  • Markus Ringnér
  • Johan Staaf

Summary, in English

A key mutational process in cancer is structural variation, in which rearrangements delete, amplify or reorder genomic segments that range in size from kilobases to whole chromosomes1-7. Here we develop methods to group, classify and describe somatic structural variants, using data from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), which aggregated whole-genome sequencing data from 2,658 cancers across 38 tumour types8. Sixteen signatures of structural variation emerged. Deletions have a multimodal size distribution, assort unevenly across tumour types and patients, are enriched in late-replicating regions and correlate with inversions. Tandem duplications also have a multimodal size distribution, but are enriched in early-replicating regions-as are unbalanced translocations. Replication-based mechanisms of rearrangement generate varied chromosomal structures with low-level copy-number gains and frequent inverted rearrangements. One prominent structure consists of 2-7 templates copied from distinct regions of the genome strung together within one locus. Such cycles of templated insertions correlate with tandem duplications, and-in liver cancer-frequently activate the telomerase gene TERT. A wide variety of rearrangement processes are active in cancer, which generate complex configurations of the genome upon which selection can act.

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

2020-02

Language

English

Pages

112-121

Publication/Series

Nature

Volume

578

Issue

7793

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Medical Genetics

Keywords

  • Gene Rearrangement/genetics
  • Genetic Variation
  • Genome, Human/genetics
  • Genomics
  • Humans
  • Mutagenesis, Insertional
  • Neoplasms/genetics
  • Telomerase/genetics

Status

Published

Research group

  • Familial Breast Cancer
  • Research Group Lung Cancer

ISBN/ISSN/Other

  • ISSN: 0028-0836