Prostate cancer (PCa) is the most frequently diagnosed male cancer. An earlier study of a cohort of 333 primary prostate carcinomas showed that 74% of these tumors fell into one of seven subtypes of a molecular taxonomy defined by specific gene fusions (ERG, ETV1/4 and FLI1) or mutations (SPOP, FOXA1 and IDH1). Molecular subtypes may aid in distinguishing indolent cases from aggressive cases and improving management of the disease. However, molecular features of PCa outside the seven subtypes are still not well studied. Here we report molecular features of PCa cases without typical features of the established subtypes. We performed comprehensive genomic analysis of 91 patients, including 54 primary and 37 metastatic cases, by whole‐exome sequencing. TP53, SPOP, FOXA1, AR (androgen receptor) and a TMPRSS2–ERG fusion emerged as the most commonly altered genes in primary cases, whereas AR, FOXA1, PTEN, CDK12, APC and TP53 were the most commonly altered genes in metastatic cases. Nuclear receptor corepressor (NCOR1) genomic alterations have been identified in 5% of cases, which are nontypical molecular features of PCa subtypes. A novel NCOR1 c.2182G>C (p.Val728Leu) was identified in tumor. RT‐PCR was used to show that this mutation caused loss of NCOR1 exon 19 and might be oncogenic in PCa. NCOR1 is involved in maintenance of mitochondrial membrane potential in PCa cells, and loss of NCOR1 might contribute to PCa progression. Therefore, NCOR1 may be a potential molecular marker of a subtype of PCa.

中文翻译：

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NCOR1可能是前列腺癌新型分子亚型的潜在生物标志物

前列腺癌 (PCa) 是最常被诊断出的男性癌症。一项对 333 例原发性前列腺癌的早期研究表明，这些肿瘤中有 74% 属于由特定基因融合（ERG、ETV1/4和FLI1）或突变（SPOP、FOXA1和IDH1）定义的分子分类法的七个亚型之一。）。分子亚型可能有助于区分惰性病例和侵袭性病例并改善疾病的管理。然而，七种亚型之外的 PCa 的分子特征仍未得到很好的研究。在这里，我们报告了 PCa 病例的分子特征，而没有既定亚型的典型特征。我们通过全外显子组测序对 91 名患者进行了全面的基因组分析，其中包括 54 名原发性和 37 名转移性病例。TP53、SPOP、FOXA1、AR（雄激素受体）和TMPRSS2 - ERG融合是原发病例中最常见的改变基因，而AR、FOXA1、PTEN、CDK12、APC和TP53是转移病例中最常见的改变基因。已在 5% 的病例中发现核受体辅助抑制因子 ( NCOR1 ) 基因组改变，这是 PCa 亚型的非典型分子特征。在肿瘤中发现了一种新的NCOR1 c.2182G>C (p.Val728Leu)。RT-PCR 用于表明该突变导致NCOR1外显子 19 的丢失，并且可能在 PCa 中具有致癌作用。NCOR1 参与维持 PCa 细胞线粒体膜电位，NCOR1 的缺失可能有助于 PCa 进展。因此，NCOR1 可能是 PCa 亚型的潜在分子标记。