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The chromatin accessibility landscape of primary human cancers
- Corces, M Ryan;
- Granja, Jeffrey M;
- Shams, Shadi;
- Louie, Bryan H;
- Seoane, Jose A;
- Zhou, Wanding;
- Silva, Tiago C;
- Groeneveld, Clarice;
- Wong, Christopher K;
- Cho, Seung Woo;
- Satpathy, Ansuman T;
- Mumbach, Maxwell R;
- Hoadley, Katherine A;
- Robertson, A Gordon;
- Sheffield, Nathan C;
- Felau, Ina;
- Castro, Mauro AA;
- Berman, Benjamin P;
- Staudt, Louis M;
- Zenklusen, Jean C;
- Laird, Peter W;
- Curtis, Christina;
- Greenleaf, William J;
- Chang, Howard Y;
- Akbani, Rehan;
- Benz, Christopher C;
- Boyle, Evan A;
- Broom, Bradley M;
- Cherniack, Andrew D;
- Craft, Brian;
- Demchok, John A;
- Doane, Ashley S;
- Elemento, Olivier;
- Ferguson, Martin L;
- Goldman, Mary J;
- Hayes, D Neil;
- He, Jing;
- Hinoue, Toshinori;
- Imielinski, Marcin;
- Jones, Steven JM;
- Kemal, Anab;
- Knijnenburg, Theo A;
- Korkut, Anil;
- Lin, De-Chen;
- Liu, Yuexin;
- Mensah, Michael KA;
- Mills, Gordon B;
- Reuter, Vincent P;
- Schultz, Andre;
- Shen, Hui;
- Smith, Jason P;
- Tarnuzzer, Roy;
- Trefflich, Sheyla;
- Wang, Zhining;
- Weinstein, John N;
- Westlake, Lindsay C;
- Xu, Jin;
- Yang, Liming;
- Yau, Christina;
- Zhao, Yang;
- Zhu, Jingchun
Published Web Location
https://doi.org/10.1126/science.aav1898Abstract
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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