The chromatin accessibility landscape of primary human cancers

M. Ryan Corces(Stanford University), Jeffrey M. Granja(Stanford University), Shadi Shams(Stanford University), Bryan H. Louie(Stanford University), José A. Seoane(Stanford University), Wanding Zhou(Van Andel Institute), Tiago C. Silva(Cedars-Sinai Medical Center), Clarice S. Groeneveld(Universidade Federal do Paraná), Christopher K. Wong(University of California, Santa Cruz), Seung Woo Cho(Stanford University), Ansuman T. Satpathy(Stanford University), Maxwell R. Mumbach(Stanford University), Katherine A. Hoadley(University of North Carolina at Chapel Hill), A. Gordon Robertson(BC Cancer Agency), Nathan C. Sheffield(University of Virginia), Ina Felau(National Cancer Institute), Mauro A. A. Castro(Universidade Federal do Paraná), Benjamin P. Berman(Cedars-Sinai Medical Center), Louis M. Staudt(National Cancer Institute), Jean C. Zenklusen(National Cancer Institute), Peter W. Laird(Van Andel Institute), Christina Curtis(Stanford University), The Cancer Genome Atlas Analysis Network(Chan Zuckerberg Initiative (United States)), William J. Greenleaf(Howard Hughes Medical Institute), Howard Y. Chang(Howard Hughes Medical Institute), Rehan Akbani, Christopher C. Benz, Evan A. Boyle, Bradley M. Broom, Andrew D. Cherniack, Brian Craft, John A. Demchok, Ashley S. Doane, Olivier Elemento, Martin L. Ferguson, Mary J. Goldman, D. Neil Hayes(University of Virginia), Jing He, Toshinori Hinoue, Marcin Imieliński, Steven J.M. Jones, Anab Kemal, Theo Knijnenburg, Anil Korkut, De‐Chen Lin, Yuexin Liu, Michael K. A. Mensah, Gordon B. Mills, Vincent Reuter, André Schultz, Hui Shen, Jason P. Smith, Roy Tarnuzzer, Sheyla Trefflich, Zhining Wang, John N. Weinstein, Lindsay Westlake, Jin Xu, Liming Yang(Stanford University), Christina Yau, Yang Zhao, Jingchun Zhu
Science
October 26, 2018
10.1126/science.aav1898
Cited by 1,321Open Access
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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.

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