Reorganization of the 3D genome pinpoints non-coding drivers of primary prostate tumors
Authors
Hawley, J. R.Zhou, S.
Arlidge, C.
Grillo, G.
Kron, K. J.
Hugh-White, R.
van der Kwast, T. H.
Fraser, M.
Boutros, P. C.
Bristow, Robert G
Lupien, M.
Affiliation
Medical Biophysics, University of Toronto, Princess Margaret Cancer Center-University Health Network, Ontario Institute for Cancer ResearchIssue Date
2021
Metadata
Show full item recordAbstract
Prostate cancer is a heterogeneous disease whose progression is linked to genome instability. However, the impact of this instability on the non-coding genome and its three-dimensional organization to aid progression is unclear. Using primary benign and tumor tissue, we find a high concordance in higher order three-dimensional genome organization. This concordance argues for constraints to the topology of prostate tumor genomes. theless, we identified changes in focal chromatin interactions, typical of loops bridging non-coding cis-regulatory elements, and showed how structural variants can induce these changes to guide cis-regulatory element hijacking. Such events resulted in opposing differential expression of genes found at antipodes of rearrangements. Collectively, these results argue that changes to focal chromatin interactions, as opposed to higher order genome organization, allow for aberrant gene regulation and are repeatedly mediated by structural variants in primary prostate cancer.Citation
Hawley JR, Zhou S, Arlidge C, Grillo G, Kron KJ, Hugh-White R, et al. Reorganization of the 3D genome pinpoints non-coding drivers of primary prostate tumors. Cancer Research. American Association for Cancer Research (AACR); 2021. p. canres.CAN-21-2056-E.2021.Journal
Cancer ResearchDOI
10.1158/0008-5472.Can-21-2056PubMed ID
34642184Additional Links
https://dx.doi.org/10.1158/0008-5472.Can-21-2056Type
ArticleLanguage
enae974a485f413a2113503eed53cd6c53
10.1158/0008-5472.Can-21-2056