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

被引：0

作者：

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

机构：

[1] University of Texas MD Anderson Cancer Center,Department of Genomic Medicine

[2] Salk Institute for Biological Studies,Division of Computational Biology

[3] Wellcome Trust Sanger Institute,Department of Medical Oncology

[4] The Jackson Laboratory for Genomic Medicine,Department of Cancer Biology

[5] Dana-Farber Cancer Institute,Department of Haematology

[6] Dana-Farber Cancer Institute,Department of Zoology, Genetics and Physical Anthropology

[7] Broad Institute of MIT and Harvard,Centre for Research in Molecular Medicine and Chronic Diseases (CIMUS)

[8] Harvard Medical School,The Biomedical Research Centre (CINBIO)

[9] University of Cambridge,Transmissible Cancer Group, Department of Veterinary Medicine

[10] Institute for Health Transformation University of Texas,Computational Biology Program

[11] Universidade de Santiago de Compostela,Department of Medical Biophysics

[12] Universidade de Santiago de Compostela,Department of Pharmacology

[13] Universidade de Vigo,Sir Peter MacCallum Department of Oncology

[14] University of Cambridge,Division of Applied Bioinformatics

[15] Ontario Institute for Cancer Research,Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine

[16] University of Toronto,Centre for Molecular Science Informatics, Department of Chemistry

[17] University of Toronto,Department of Biomedical Informatics

[18] University of California Los Angeles,Ludwig Center

[19] Peter MacCallum Cancer Centre,Cancer Research UK Cambridge Institute

[20] University of Melbourne,Sir Peter MacCallum Department of Oncology

[21] German Cancer Research Center (DKFZ),Queensland Centre for Medical Genomics, Institute for Molecular Bioscience

[22] German Cancer Consortium (DKTK),The Azrieli Faculty of Medicine

[23] National Center for Tumor Diseases (NCT) Heidelberg,Department of Computer Science

[24] Johns Hopkins School of Medicine,Department of Computer Science

[25] University of Ottawa,Department of Molecular Biophysics and Biochemistry

[26] University of Texas MD Anderson Cancer Center,Program in Computational Biology and Bioinformatics

[27] University of Cambridge,Genome Integrity and Structural Biology Laboratory

[28] Harvard Medical School,Biomolecular Engineering Department

[29] Harvard Medical School,Heidelberg Center for Personalized Oncology (DKFZ

[30] Barcelona Supercomputing Center (BSC),HIPO)

[31] University of Cambridge,Pediatric Glioma Research Group

[32] University of Cambridge,Dmitry Rogachev National Research Center of Pediatric Hematology

[33] Sidra Medicine,Integrative Bioinformatics Support Group

[34] The University of Melbourne,Center For Medical Innovation

[35] The University of Queensland,Department of Internal Medicine

[36] Bar-Ilan University,European Molecular Biology Laboratory

[37] Princeton University,Genome Biology Unit

[38] Yale University,Division of Genetics and Genomics

[39] Yale University,School of Medicine/School of Mathematics and Statistics

[40] Yale University,Department of Physiology and Biophysics

[41] National Institute of Environmental Health Sciences (NIEHS),Englander Institute for Precision Medicine

[42] University of California,Institute for Computational Biomedicine

[43] Santa Cruz,Department of Medical Oncology, Inselspital

[44] Brandeis University,Department of Pathology

[45] Massachusetts General Hospital Center for Cancer Research,The Institute of Medical Science

[46] German Cancer Research Center (DKFZ),Centre for Genomic Regulation (CRG)

[47] New York Genome Center,Institute of Medical Genetics and Applied Genomics

[48] Weill Cornell Medicine,Department of Genetics and Computational Biology

[49] Hopp Children’s Cancer Center (KiTZ),Institute for Molecular Bioscience

[50] German Cancer Research Center (DKFZ),School of Molecular Biosciences and Center for Reproductive Biology

来源：

Nature Genetics | 2020年 / 52卷

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中图分类号：

学科分类号：

摘要：

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.

引用

页码：294 / 305

页数：11

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