Department of Medicine, Boston University School of Medicine, Boston, Massachusetts.
Division of Hematology/Oncology, Department of Medicine; Helen Diller Family Comprehensive Cancer Center; Bakar Computational Health Sciences Institute; Institute for Human Genetics; San Francisco Veterans Affairs Medical Center; University of California, San Francisco, San Francisco, California.
Clin Cancer Res. 2020 Sep 1;26(17):4651-4660. doi: 10.1158/1078-0432.CCR-19-4112. Epub 2020 Jul 10.
African American (AFR) men have the highest mortality rate from prostate cancer (PCa) compared with men of other racial/ancestral groups. Differences in the spectrum of somatic genome alterations in tumors between AFR men and other populations have not been well-characterized due to a lack of inclusion of significant numbers in genomic studies.
To identify genomic alterations associated with race, we compared the frequencies of somatic alterations in PCa obtained from four publicly available datasets comprising 250 AFR and 611 European American (EUR) men and a targeted sequencing dataset from a commercial platform of 436 AFR and 3018 EUR men.
Mutations in as well as focal deletions in were more frequent in tumors from AFR men. mutations were associated with increasing Gleason score. amplifications were more frequent in tumors from AFR men with metastatic PCa, whereas deletions in and rearrangements in were less frequent in tumors from AFR men. truncations and amplifications were more frequent in primary PCa from AFR men. Genomic features that could impact clinical decision making were not significantly different between the two groups including tumor mutation burden, MSI status, and genomic alterations in select DNA repair genes, , and in .
Although we identified some novel differences in AFR men compared with other populations, the frequencies of genomic alterations in current therapeutic targets for PCa were similar between AFR and EUR men, suggesting that existing precision medicine approaches could be equally beneficial if applied equitably.
与其他种族/祖先群体的男性相比，非裔美国男性（AFR）的前列腺癌（PCa）死亡率最高。由于在基因组研究中缺乏大量的纳入，因此尚未很好地描述 AFR 男性与其他人群之间肿瘤中体细胞基因组改变的谱差异。
为了确定与种族相关的基因组改变，我们比较了来自四个公开可用数据集的 PCa 中体细胞改变的频率，这些数据集包括 250 名 AFR 和 611 名欧洲裔美国（EUR）男性，以及来自商业平台的 436 名 AFR 和 3018 名 EUR 男性的靶向测序数据集。
中的突变以及 中的局灶性缺失在 AFR 男性的肿瘤中更为频繁。 突变与 Gleason 评分的增加相关。 扩增在 AFR 男性转移性 PCa 肿瘤中更为常见，而 中的缺失和 中的重排在 AFR 男性肿瘤中则较少见。 截短和 扩增在 AFR 男性的原发性 PCa 中更为常见。可能影响临床决策的基因组特征在两组之间没有显著差异，包括肿瘤突变负担、MSI 状态以及在 、 和 中选择的 DNA 修复基因中的基因组改变。
尽管我们与其他人群相比在 AFR 男性中发现了一些新的差异，但当前 PCa 治疗靶点的基因组改变频率在 AFR 和 EUR 男性之间相似，这表明如果公平应用，现有的精准医学方法同样有益。
