The chromatin accessibility landscape of primary human cancers

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; William J. Greenleaf; Howard Y. Chang

doi:https://doi.org/10.1126/science.aav1898

The chromatin accessibility landscape of primary human cancers

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. ZenklusenPeter W. Laird, Christina Curtis, William J. Greenleaf, Howard Y. Chang

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	eaav1898
Journal	Science
Volume	362
Issue number	6413
DOIs	https://doi.org/10.1126/science.aav1898
State	Published - 26 Oct 2018
Externally published	Yes

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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Corces, M. R., Granja, J. M., Shams, S., Louie, B. H., Seoane, J. A., Zhou, W., Silva, T. C., Groeneveld, C., Wong, C. K., Cho, S. W., Satpathy, A. T., Mumbach, M. R., Hoadley, K. A., Robertson, A. G., Sheffield, N. C., Felau, I., Castro, M. A. A., Berman, B. P., Staudt, L. M., ... Chang, H. Y. (2018). The chromatin accessibility landscape of primary human cancers. Science, 362(6413), Article eaav1898. https://doi.org/10.1126/science.aav1898

@article{e5ff01b3b3d64785bed48347368a01fc,

title = "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.",

author = "Corces, {M. Ryan} and Granja, {Jeffrey M.} and Shadi Shams and Louie, {Bryan H.} and Seoane, {Jose A.} and Wanding Zhou and Silva, {Tiago C.} and Clarice Groeneveld and Wong, {Christopher K.} and Cho, {Seung Woo} and Satpathy, {Ansuman T.} and Mumbach, {Maxwell R.} and Hoadley, {Katherine A.} and Robertson, {A. Gordon} and Sheffield, {Nathan C.} and Ina Felau and Castro, {Mauro A.A.} and Berman, {Benjamin P.} and Staudt, {Louis M.} and Zenklusen, {Jean C.} and Laird, {Peter W.} and Christina Curtis and Greenleaf, {William J.} and Chang, {Howard Y.}",

year = "2018",

month = oct,

day = "26",

doi = "https://doi.org/10.1126/science.aav1898",

language = "الإنجليزيّة",

volume = "362",

journal = "Science",

issn = "0036-8075",

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number = "6413",

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Corces, MR, Granja, JM, Shams, S, Louie, BH, Seoane, JA, Zhou, W, Silva, TC, Groeneveld, C, Wong, CK, Cho, SW, Satpathy, AT, Mumbach, MR, Hoadley, KA, Robertson, AG, Sheffield, NC, Felau, I, Castro, MAA, Berman, BP, Staudt, LM, Zenklusen, JC, Laird, PW, Curtis, C, Greenleaf, WJ & Chang, HY 2018, 'The chromatin accessibility landscape of primary human cancers', Science, vol. 362, no. 6413, eaav1898. https://doi.org/10.1126/science.aav1898

TY - JOUR

T1 - The chromatin accessibility landscape of primary human cancers

AU - Corces, M. Ryan

AU - Granja, Jeffrey M.

AU - Shams, Shadi

AU - Louie, Bryan H.

AU - Seoane, Jose A.

AU - Zhou, Wanding

AU - Silva, Tiago C.

AU - Groeneveld, Clarice

AU - Wong, Christopher K.

AU - Cho, Seung Woo

AU - Satpathy, Ansuman T.

AU - Mumbach, Maxwell R.

AU - Hoadley, Katherine A.

AU - Robertson, A. Gordon

AU - Sheffield, Nathan C.

AU - Felau, Ina

AU - Castro, Mauro A.A.

AU - Berman, Benjamin P.

AU - Staudt, Louis M.

AU - Zenklusen, Jean C.

AU - Laird, Peter W.

AU - Curtis, Christina

AU - Greenleaf, William J.

AU - Chang, Howard Y.

PY - 2018/10/26

Y1 - 2018/10/26

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85055613174&partnerID=8YFLogxK

U2 - https://doi.org/10.1126/science.aav1898

DO - https://doi.org/10.1126/science.aav1898

M3 - مقالة

C2 - 30361341

SN - 0036-8075

VL - 362

JO - Science

JF - Science

IS - 6413

M1 - eaav1898

ER -

The chromatin accessibility landscape of primary human cancers

Abstract

All Science Journal Classification (ASJC) codes

UN SDGs

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