Cistrome partitioning reveals convergence of somatic mutations and risk variants on master transcription regulators in primary prostate tumors
Authors
Mazrooei, PKron, 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, Robert G
Zwart, W
Lupien, M
Affiliation
Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, CanadaIssue Date
2019
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Show full item recordAbstract
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.Citation
Mazrooei P, Kron KJ, Zhu Y, Zhou S, Grillo G, Mehdi T, et al. Cistrome Partitioning Reveals Convergence of Somatic Mutations and Risk Variants on Master Transcription Regulators in Primary Prostate Tumors. Cancer Cell. 2019.Journal
Cancer CellDOI
10.1016/j.ccell.2019.10.005PubMed ID
31735626Additional Links
https://dx.doi.org/10.1016/j.ccell.2019.10.005Type
ArticleLanguage
enae974a485f413a2113503eed53cd6c53
10.1016/j.ccell.2019.10.005
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