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Åke Borg

Åke Borg

Principal investigator

Åke Borg

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

Author

  • Kadir C Akdemir
  • Victoria T Le
  • Sahaana Chandran
  • Yilong Li
  • Roel G Verhaak
  • Rameen Beroukhim
  • Peter J Campbell
  • Lynda Chin
  • Jesse R Dixon
  • P Andrew Futreal

Other contributions

  • Åke Borg
  • Markus Ringnér
  • Johan Staaf

Summary, in English

Chromatin is folded into successive layers to organize linear DNA. Genes within the same topologically associating domains (TADs) demonstrate similar expression and histone-modification profiles, and boundaries separating different domains have important roles in reinforcing the stability of these features. Indeed, domain disruptions in human cancers can lead to misregulation of gene expression. However, the frequency of domain disruptions in human cancers remains unclear. 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), which aggregated whole-genome sequencing data from 2,658 cancers across 38 tumor types, we analyzed 288,457 somatic structural variations (SVs) to understand the distributions and effects of SVs across TADs. Notably, SVs can lead to the fusion of discrete TADs, and complex rearrangements markedly change chromatin folding maps in the cancer genomes. Notably, only 14% of the boundary deletions resulted in a change in expression in nearby genes of more than twofold.

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

294-305

Publication/Series

Nature Genetics

Volume

52

Issue

3

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Medical Genetics

Keywords

  • Chromatin/genetics
  • Gene Expression Regulation, Neoplastic
  • Gene Rearrangement/genetics
  • Genome, Human/genetics
  • Genomic Structural Variation
  • Humans
  • Neoplasms/genetics

Status

Published

Research group

  • Familial Breast Cancer
  • Research Group Lung Cancer

ISBN/ISSN/Other

  • ISSN: 1546-1718