Cistrome Partitioning Reveals Convergence of Somatic Mutations and Risk Variants on Master Transcription Regulators in Primary Prostate Tumors

Parisa Mazrooei; Ken J Kron; Yanyun Zhu; Stanley Zhou; Giacomo Grillo; Tahmid Mehdi; Musaddeque Ahmed; Tesa M Severson; Paul Guilhamon; Nicholas Sinnott Armstrong; Vincent Huang; Takafumi N Yamaguchi; Michael Fraser; Theodorus van der Kwast; Paul C Boutros; Housheng Hansen He; Andries M Bergman; Robert G Bristow; Wilbert Zwart; Mathieu Lupien

doi:10.1016/j.ccell.2019.10.005

Cistrome Partitioning Reveals Convergence of Somatic Mutations and Risk Variants on Master Transcription Regulators in Primary Prostate Tumors

Parisa Mazrooei, Ken J Kron, Yanyun Zhu, Stanley Zhou, Giacomo Grillo, Tahmid Mehdi, Musaddeque Ahmed, Tesa M Severson, Paul Guilhamon, Nicholas Sinnott Armstrong, Vincent Huang, Takafumi N Yamaguchi, Michael Fraser, Theodorus van der Kwast, Paul C Boutros, Housheng Hansen He, Andries M Bergman, Robert G Bristow, Wilbert Zwart, Mathieu Lupien

Division of Cancer Sciences (L5)

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

Abstract

Thousands of noncoding somatic single-nucleotide variants (SNVs) of unknown function are reported in tumors. Partitioning the genome according to cistromes reveals the enrichment of somatic SNVs in prostate tumors as opposed to adjacent normal tissue cistromes of master transcription regulators, including AR, FOXA1, and HOXB13. This parallels enrichment of prostate cancer genetic predispositions over these transcription regulators' tumor cistromes, exemplified at the 8q24 locus harboring both risk variants and somatic SNVs in cis-regulatory elements upregulating MYC expression. However, Massively Parallel Reporter Assays reveal that few SNVs can alter the transactivation potential of individual cis-regulatory elements. Instead, similar to inherited risk variants, SNVs accumulate in cistromes of master transcription regulators required for prostate cancer development.

Original language	English
Pages (from-to)	674-689.e6
Journal	Cancer Cell
Volume	36
Issue number	6
Early online date	14 Nov 2019
DOIs	https://doi.org/10.1016/j.ccell.2019.10.005
Publication status	Published - 9 Dec 2019

Research Beacons, Institutes and Platforms

Manchester Cancer Research Centre

UN SDGs

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

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10.1016/j.ccell.2019.10.005

https://www.sciencedirect.com/science/article/pii/S1535610819304799

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Mazrooei, P., Kron, K. J., Zhu, Y., Zhou, S., Grillo, G., Mehdi, T., Ahmed, M., Severson, T. M., Guilhamon, P., Armstrong, N. S., Huang, V., Yamaguchi, T. N., Fraser, M., van der Kwast, T., Boutros, P. C., He, H. H., Bergman, A. M., Bristow, R. G., Zwart, W., & Lupien, M. (2019). Cistrome Partitioning Reveals Convergence of Somatic Mutations and Risk Variants on Master Transcription Regulators in Primary Prostate Tumors. Cancer Cell, 36(6), 674-689.e6. https://doi.org/10.1016/j.ccell.2019.10.005

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title = "Cistrome Partitioning Reveals Convergence of Somatic Mutations and Risk Variants on Master Transcription Regulators in Primary Prostate Tumors",

abstract = "Thousands of noncoding somatic single-nucleotide variants (SNVs) of unknown function are reported in tumors. Partitioning the genome according to cistromes reveals the enrichment of somatic SNVs in prostate tumors as opposed to adjacent normal tissue cistromes of master transcription regulators, including AR, FOXA1, and HOXB13. This parallels enrichment of prostate cancer genetic predispositions over these transcription regulators' tumor cistromes, exemplified at the 8q24 locus harboring both risk variants and somatic SNVs in cis-regulatory elements upregulating MYC expression. However, Massively Parallel Reporter Assays reveal that few SNVs can alter the transactivation potential of individual cis-regulatory elements. Instead, similar to inherited risk variants, SNVs accumulate in cistromes of master transcription regulators required for prostate cancer development.",

author = "Parisa Mazrooei and Kron, {Ken J} and Yanyun Zhu and Stanley Zhou and Giacomo Grillo and Tahmid Mehdi and Musaddeque Ahmed and Severson, {Tesa M} and Paul Guilhamon and Armstrong, {Nicholas Sinnott} and Vincent Huang and Yamaguchi, {Takafumi N} and Michael Fraser and {van der Kwast}, Theodorus and Boutros, {Paul C} and He, {Housheng Hansen} and Bergman, {Andries M} and Bristow, {Robert G} and Wilbert Zwart and Mathieu Lupien",

year = "2019",

month = dec,

day = "9",

doi = "10.1016/j.ccell.2019.10.005",

language = "English",

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Mazrooei, P, Kron, KJ, Zhu, Y, Zhou, S, Grillo, G, Mehdi, T, Ahmed, M, Severson, TM, Guilhamon, P, Armstrong, NS, Huang, V, Yamaguchi, TN, Fraser, M, van der Kwast, T, Boutros, PC, He, HH, Bergman, AM, Bristow, RG, Zwart, W & Lupien, M 2019, 'Cistrome Partitioning Reveals Convergence of Somatic Mutations and Risk Variants on Master Transcription Regulators in Primary Prostate Tumors', Cancer Cell, vol. 36, no. 6, pp. 674-689.e6. https://doi.org/10.1016/j.ccell.2019.10.005

TY - JOUR

T1 - Cistrome Partitioning Reveals Convergence of Somatic Mutations and Risk Variants on Master Transcription Regulators in Primary Prostate Tumors

AU - Mazrooei, Parisa

AU - Kron, Ken J

AU - Zhu, Yanyun

AU - Zhou, Stanley

AU - Grillo, Giacomo

AU - Mehdi, Tahmid

AU - Ahmed, Musaddeque

AU - Severson, Tesa M

AU - Guilhamon, Paul

AU - Armstrong, Nicholas Sinnott

AU - Huang, Vincent

AU - Yamaguchi, Takafumi N

AU - Fraser, Michael

AU - van der Kwast, Theodorus

AU - Boutros, Paul C

AU - He, Housheng Hansen

AU - Bergman, Andries M

AU - Bristow, Robert G

AU - Zwart, Wilbert

AU - Lupien, Mathieu

PY - 2019/12/9

Y1 - 2019/12/9

N2 - Thousands of noncoding somatic single-nucleotide variants (SNVs) of unknown function are reported in tumors. Partitioning the genome according to cistromes reveals the enrichment of somatic SNVs in prostate tumors as opposed to adjacent normal tissue cistromes of master transcription regulators, including AR, FOXA1, and HOXB13. This parallels enrichment of prostate cancer genetic predispositions over these transcription regulators' tumor cistromes, exemplified at the 8q24 locus harboring both risk variants and somatic SNVs in cis-regulatory elements upregulating MYC expression. However, Massively Parallel Reporter Assays reveal that few SNVs can alter the transactivation potential of individual cis-regulatory elements. Instead, similar to inherited risk variants, SNVs accumulate in cistromes of master transcription regulators required for prostate cancer development.

AB - Thousands of noncoding somatic single-nucleotide variants (SNVs) of unknown function are reported in tumors. Partitioning the genome according to cistromes reveals the enrichment of somatic SNVs in prostate tumors as opposed to adjacent normal tissue cistromes of master transcription regulators, including AR, FOXA1, and HOXB13. This parallels enrichment of prostate cancer genetic predispositions over these transcription regulators' tumor cistromes, exemplified at the 8q24 locus harboring both risk variants and somatic SNVs in cis-regulatory elements upregulating MYC expression. However, Massively Parallel Reporter Assays reveal that few SNVs can alter the transactivation potential of individual cis-regulatory elements. Instead, similar to inherited risk variants, SNVs accumulate in cistromes of master transcription regulators required for prostate cancer development.

U2 - 10.1016/j.ccell.2019.10.005

DO - 10.1016/j.ccell.2019.10.005

M3 - Article

C2 - 31735626

SN - 1535-6108

VL - 36

SP - 674-689.e6

JO - Cancer Cell

JF - Cancer Cell

IS - 6

ER -

Cistrome Partitioning Reveals Convergence of Somatic Mutations and Risk Variants on Master Transcription Regulators in Primary Prostate Tumors

Abstract

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UN SDGs

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