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: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

^*Corresponding author for this work

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

657 Scopus citations

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

Bibliographical note

Publisher Copyright:
© 2018 Institute of Physics Publishing. All rights reserved.

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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

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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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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

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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

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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.

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The chromatin accessibility landscape of primary human cancers

Abstract

Bibliographical note

UN SDGs

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