American Association for Cancer Research
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Supplementary Figure 3 from Reorganization of the 3D Genome Pinpoints Noncoding Drivers of Primary Prostate Tumors

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posted on 2023-03-31, 05:01 authored by James R. Hawley, Stanley Zhou, Christopher Arlidge, Giacomo Grillo, Ken J. Kron, Rupert Hugh-White, Theodorus H. van der Kwast, Michael Fraser, Paul C. Boutros, Robert G. Bristow, Mathieu Lupien

Characterization of chromatin interactions in benign and tumour tissue.


Prostate Cancer Foundation Canada

Ontario Institute for Cancer Research funded by the Government of Ontario

Princess Margaret Cancer Foundation

Princess Margaret Cancer Centre Department of Surgical Oncology

Princess Margaret Cancer Centre Genetics and Epigenetic Program

University of Toronto Department of Surgery Division of Urology

Movember Foundation

Radiation Medicine Program Academic Enrichment Fund

Terry Fox Research Institute New Investigator Award

Canadian Institute of Health Research

New Investigator Award

Canadian Cancer Society Research Scientist Award

Cancer Society Impact Award

Investigator Award from the Ontario Institute for Cancer Research

Movember Rising Star Award from PCa Canada



Prostate cancer is a heterogeneous disease whose progression is linked to genome instability. However, the impact of this instability on the noncoding 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. Nonetheless, we identified changes in focal chromatin interactions, typical of loops bridging noncoding 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. This work showcases how the noncoding genome can be hijacked by focal insults to its three-dimensional organization that contribute to prostate cancer oncogenesis.

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