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. Significance: 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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3D 基因组的重组确定了原发性前列腺肿瘤的非编码驱动因素

前列腺癌是一种异质性疾病，其进展与基因组不稳定性有关。然而，这种不稳定性对非编码基因组及其促进进展的三维组织的影响尚不清楚。使用原发性良性和肿瘤组织，我们发现高阶三维基因组组织具有高度一致性。这种一致性证明了对前列腺肿瘤基因组拓扑结构的限制。尽管如此，我们确定了焦点染色质相互作用的变化，典型的环桥接非编码顺式调节元件，并展示了结构变异如何诱导这些变化以指导顺式调节元件劫持。这些事件导致在重排的对端发现的基因的相反差异表达。总的来说，这些结果表明焦点染色质相互作用的变化，与高阶基因组组织相反，它允许异常的基因调控，并由原发性前列腺癌的结构变异反复介导。意义：这项工作展示了非编码基因组如何被局部损伤劫持，从而导致前列腺癌的肿瘤发生。