The chromatin accessibility landscape of primary human cancers.

Abstract

We present the genome-wide chromatin accessibility profiles of 410 tumor samples spanning 23 cancer types from The Cancer Genome Atlas (TCGA). We identify 562,709 transposase-accessible DNA elements that substantially extend the compendium of known cis-regulatory elements. Integration of ATAC-seq (the assay for transposase-accessible chromatin using sequencing) with TCGA multi-omic data identifies a large number of putative distal enhancers that distinguish molecular subtypes of cancers, uncovers specific driving transcription factors via protein-DNA footprints, and nominates long-range gene-regulatory interactions in cancer. These data reveal genetic risk loci of cancer predisposition as active DNA regulatory elements in cancer, identify gene-regulatory interactions underlying cancer immune evasion, and pinpoint noncoding mutations that drive enhancer activation and may affect patient survival. These results suggest a systematic approach to understanding the noncoding genome in cancer to advance diagnosis and therapy.

• Authors: M Ryan Corces, Jeffrey M Granja, Shadi Shams, Bryan H Louie, Jose A Seoane, Wanding Zhou, Tiago C Silva, Clarice Groeneveld, Christopher K Wong, Seung Woo Cho, Ansuman T Satpathy, Maxwell R Mumbach, Katherine A Hoadley, A Gordon Robertson, Nathan C Sheffield, Ina Felau, Mauro A A Castro, Benjamin P Berman, Louis M Staudt, Jean C Zenklusen, Peter W Laird, Christina Curtis, Cancer Genome Atlas Analysis Network, William J Greenleaf, Howard Y Chang
• Journal: Science (New York, N.Y.) (Science) Vol. 362 Issue 6413 (10 26 2018) ISSN: 1095-9203 [Electronic] United States
• PMID: 30361341 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Chemical References

• Chromatin
• Transcription Factors
• Transposases

Topics

• Chromatin (genetics, metabolism)
• DNA Footprinting
• Enhancer Elements, Genetic
• Gene Expression Regulation, Neoplastic
• Genetic Loci
• Genetic Predisposition to Disease
• Humans
• Immunity (genetics)
• Neoplasms (genetics, metabolism)
• Regulatory Sequences, Nucleic Acid
• Transcription Factors (metabolism)
• Transposases (metabolism)