Garvan Institute of Medical Research, The Kinghorn Cancer Centre, Darlinghurst, Australia.
St. Vincent's Clinical School, Faculty of Medicine, UNSW, Sydney, Australia.
Prostate. 2019 Jul;79(10):1191-1196. doi: 10.1002/pros.23823. Epub 2019 May 15.
The androgen-regulated gene TMPRSS2 to the ETS transcription factor gene ERG fusion is the most common genomic alteration acquired during prostate tumorigenesis and biased toward men of European ancestry. In contrast, African American men present with more advanced disease, yet their tumors are less likely to acquire TMPRSS2-ERG. Data for Africa is scarce.
RNA was made available for genomic analyses from 181 prostate tissue biopsy cores from Black South African men, 94 with and 87 without pathological evidence for prostate cancer. Reverse transcription polymerase chain reaction was used to screen for the TMPRSS2-ERG fusion, while transcript junction coordinates and isoform frequencies, including novel gene fusions, were determined using targeted RNA sequencing.
Here we report a frequency of 13% for TMPRSS2-ERG in tumors from Black South Africans. Present in 12/94 positive versus 1/87 cancer negative prostate tissue cores, this suggests a 92.62% predictivity for a positive cancer diagnosis (P = 0.0031). At a frequency of almost half that reported for African Americans and roughly a quarter of that reported for men of European ancestry, acquisition of TMPRSS2-ERG appears to be inversely associated with aggressive prostate cancer. Further support was provided by linking the presence of TMPRSS2-ERG to low-grade disease in younger patients (P = 0.0466), with higher expressing distal ERG fusion junction coordinates.
Only the second study of its kind for the African continent, we support a link between TMPRSS2-ERG status and prostate cancer racial health disparity beyond the borders of the United States. We call for urgent evaluation of androgen deprivation therapy within Africa.
雄激素调节基因 TMPRSS2 与 ETS 转录因子基因 ERG 融合是前列腺肿瘤发生过程中最常见的基因组改变，且偏向于欧洲血统的男性。相比之下，非裔美国男性表现出更晚期的疾病，但他们的肿瘤不太可能获得 TMPRSS2-ERG。非洲的数据稀缺。
从 181 个南非黑人男性的前列腺组织活检核心中获得了用于基因组分析的 RNA，其中 94 个有和 87 个没有前列腺癌的病理证据。使用逆转录聚合酶链式反应筛选 TMPRSS2-ERG 融合，同时使用靶向 RNA 测序确定转录接头坐标和异构体频率，包括新的基因融合。
我们在此报告南非黑人肿瘤中 TMPRSS2-ERG 的频率为 13%。在 12/94 个阳性与 1/87 个癌症阴性的前列腺组织核心中存在，这表明阳性癌症诊断的预测性为 92.62%（P=0.0031）。其频率接近非裔美国人报告的一半，略低于欧洲裔祖先报告的四分之一，获得 TMPRSS2-ERG 似乎与侵袭性前列腺癌呈负相关。通过将 TMPRSS2-ERG 的存在与年轻患者的低级别疾病联系起来，进一步支持了这一观点（P=0.0466），与远端 ERG 融合接头坐标表达较高有关。
这是非洲大陆同类研究中的第二项研究，我们支持 TMPRSS2-ERG 状态与美国境外前列腺癌种族健康差异之间的联系。我们呼吁在非洲紧急评估雄激素剥夺疗法。
