以染色体数量不平衡为特征的较高水平的非整倍性与前列腺癌的致命进展相关。然而，非整倍体如何导致前列腺癌的侵袭性仍然知之甚少。在这项研究中，我们在患者中评估了 8q 染色体（前列腺肿瘤中最常见的染色体臂之一）上的哪些基因与癌症进展为转移和前列腺癌（致死性疾病）死亡的长期风险最密切相关。 403 名患者，发现最强的候选者是粘连蛋白亚基基因 RAD21，比较 mRNA 表达的最高与最低三分位数并调整总体非整倍性负担和格里森评分，优势比为 3.7（95% CI 1.8，7.6），两者均很强原发性前列腺癌的预后因素。在研究约一半前列腺肿瘤中发现的由 TMPRSS2-ERG 致癌融合驱动的前列腺癌时，我们发现 RAD21 的增加减轻了有毒致癌应激和由致癌基因表达引起的 DNA 损伤。来自类器官和患者的数据表明，RAD21 的增加从而使侵袭性肿瘤能够维持肿瘤增殖，并且更广泛地表明肿瘤从非整倍性中受益的一种途径。

Higher levels of aneuploidy, characterized by imbalanced chromosome numbers, are associated with lethal progression in prostate cancer. However, how aneuploidy contributes to prostate cancer aggressiveness remains poorly understood. In this study, we assessed in patients which genes on chromosome 8q, one of the most frequently gained chromosome arms in prostate tumors, were most strongly associated with long-term risk of cancer progression to metastases and death from prostate cancer (lethal disease) in 403 patients and found the strongest candidate was cohesin subunit gene, RAD21, with an odds ratio of 3.7 (95% CI 1.8, 7.6) comparing the highest vs. lowest tertiles of mRNA expression and adjusting for overall aneuploidy burden and Gleason score, both strong prognostic factors in primary prostate cancer. Studying prostate cancer driven by the TMPRSS2-ERG oncogenic fusion, found in about half of all prostate tumors, we found that increased RAD21 alleviated toxic oncogenic stress and DNA damage caused by oncogene expression. Data from both organoids and patients indicate that increased RAD21 thereby enables aggressive tumors to sustain tumor proliferation, and more broadly suggests one path through which tumors benefit from aneuploidy.