Åke Borg
Principal investigator
Disruption of chromatin folding domains by somatic genomic rearrangements in human cancer
Author
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