The chromatin accessibility landscape of primary human cancers
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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 A. A.; Berman, Benjamin P.; Staudt, Louis M.; Zenklusen, Jean C.; Laird, Peter W.; Curtis, Christina; Greenleaf, William J.; Chang, Howard Y.
- Issue Date
- AMER ASSOC ADVANCEMENT SCIENCE
- SCIENCE, v.362, no.6413, pp.420
- 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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