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

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

    Research output: Contribution to journalJournal articleResearchpeer-review

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

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

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

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

    Research output: Contribution to journalJournal articleResearchpeer-review

  • PCAWG-Structural Variation Working Group
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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.

Original languageEnglish
JournalNature Genetics
Volume52
Issue number3
Pages (from-to)294-305
Number of pages12
ISSN1061-4036
DOIs
Publication statusPublished - Mar 2020
Externally publishedYes

    Research areas

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

ID: 59265807