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Åke Borg

Åke Borg

Principal investigator

Åke Borg

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

Author

  • Isidro Cortés-Ciriano
  • Jake June-Koo Lee
  • Ruibin Xi
  • Dhawal Jain
  • Youngsook L Jung
  • Lixing Yang
  • Dmitry Gordenin
  • Leszek J Klimczak
  • Cheng-Zhong Zhang
  • David S Pellman
  • Peter J Park
Show all

Other contributions

  • Åke Borg
  • Markus Ringnér
  • Johan Staaf

Summary, in English

Chromothripsis is a mutational phenomenon characterized by massive, clustered genomic rearrangements that occurs in cancer and other diseases. Recent studies in selected cancer types have suggested that chromothripsis may be more common than initially inferred from low-resolution copy-number data. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we analyze patterns of chromothripsis across 2,658 tumors from 38 cancer types using whole-genome sequencing data. We find that chromothripsis events are pervasive across cancers, with a frequency of more than 50% in several cancer types. Whereas canonical chromothripsis profiles display oscillations between two copy-number states, a considerable fraction of events involve multiple chromosomes and additional structural alterations. In addition to non-homologous end joining, we detect signatures of replication-associated processes and templated insertions. Chromothripsis contributes to oncogene amplification and to inactivation of genes such as mismatch-repair-related genes. These findings show that chromothripsis is a major process that drives genome evolution in human cancer.

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

331-341

Publication/Series

Nature Genetics

Volume

52

Issue

3

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Medical Genetics

Keywords

  • Chromothripsis
  • Evolution, Molecular
  • Genome, Human/genetics
  • Genomics
  • Humans
  • Mutation
  • Neoplasms/genetics
  • Whole Genome Sequencing

Status

Published

Research group

  • Familial Breast Cancer
  • Research Group Lung Cancer

ISBN/ISSN/Other

  • ISSN: 1546-1718