The chromatin accessibility landscape of primary human cancers

被引：743

作者：

Corces, M. Ryan ^{[1
]}

Granja, Jeffrey M. ^{[1
,2
,3
]}

Shams, Shadi ^{[1
]}

Louie, Bryan H. ^{[1
]}

Seoane, Jose A. ^{[2
,4
,5
]}

Zhou, Wanding ^{[6
]}

Silva, Tiago C. ^{[7
,8
]}

Groeneveld, Clarice ^{[9
]}

Wong, Christopher K. ^{[10
]}

Cho, Seung Woo ^{[1
]}

Satpathy, Ansuman T. ^{[1
]}

Mumbach, Maxwell R. ^{[1
,2
]}

Hoadley, Katherine A. ^{[11
]}

Robertson, A. Gordon ^{[12
]}

Sheffield, Nathan C. ^{[13
]}

Felau, Ina

Castro, Mauro A. A.

Berman, Benjamin P. ^{[7
]}

Staudt, Louis M. ^{[14
]}

Zenklusen, Jean C. ^{[14
]}

Laird, Peter W.

Curtis, Christina ^{[2
,4
,5
]}

Greenleaf, William J. ^{[1
,2
,3
,15
,16
]}

Chang, Howard Y. ^{[1
,2
,17
,18
]}

机构：

[1] Stanford Univ, Ctr Personal Dynam Regulomes, Stanford, CA 94305 USA

[2] Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA

[3] Stanford Univ, Sch Med, Program Biophys, Stanford, CA 94305 USA

[4] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA

[5] Stanford Univ, Sch Med, Stanford Canc Inst, Stanford, CA 94305 USA

[6] Van Andel Res Inst, Ctr Epigenet, Grand Rapids, MI 49503 USA

[7] Cedars Sinai Med Ctr, Ctr Bioinformat & Funct Genom, Los Angeles, CA 90048 USA

[8] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Genet, BR-14040905 Ribeirao Preto, SP, Brazil

[9] Univ Fed Parana, Polytech Ctr, Bioinformat & Syst Biol Lab, BR-80060000 Curitiba, PR, Brazil

[10] Univ Calif Santa Cruz, Ctr Biomol Sci & Engn, Dept Biomol Engn, Santa Cruz, CA 95064 USA

[11] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Genet, Chapel Hill, NC 27599 USA

[12] BC Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 4S6, Canada

[13] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA 22908 USA

[14] NCI, NIH, Bethesda, MD 20892 USA

[15] Stanford Univ, Dept Appl Sci, Menlo Pk, CA 94025 USA

[16] Chan Zuckerberg Biohub, San Francisco, CA 94158 USA

[17] Stanford Univ, Program Epithelial Biol, Stanford, CA 94305 USA

[18] Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA

来源：

SCIENCE | 2018年 / 362卷 / 6413期

关键词：

GENOME-WIDE ASSOCIATION; ENHANCER; REVEALS; BINDING; TUMORS; METHYLOME; CRISPR; RISK;

D O I：

10.1126/science.aav1898

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：420 / +

页数：14

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