Project 3: Integrative and Functional Genomics of Aggressive Prostate Cancer in African American Men

摘要-项目3 长期以来，人们已经知道，非裔美国人男性患上 与其他种族的男性相比，前列腺癌的发病率更高。社会经济因素和不平等的保健机会 护理无疑是造成这种差异的原因；然而，在以下情况下，发病率和结局仍然存在差异 考虑到这些因素。这增加了一种可能性，即肿瘤生物学和/或基因改变的差异 也会导致与非裔美国人前列腺癌有关的不良后果。的总体目标是 这项计划是全面询问突变景观和致癌基因的表达模式 存在于原发的非裔美国人前列腺癌。为此，我们将描述~3,000个肿瘤 使用完整外显子组测序和靶向测序的响应队列中的样本。大致 其中1000个肿瘤也将接受转录组分析。这些数据将被用来研究这种关系 前列腺癌基因和肿瘤侵袭性之间的关系，并将与 欧洲血统，以确定是否有任何基因或转录变化表现出不同的患病率 作为祖先的一种功能。此外，我们将使用原代前列腺上皮细胞的体外研究来测试 常见的前列腺癌改变在引入非恶性疾病时具有更强的致瘤作用 非裔美国男性的前列腺细胞与白人男性的前列腺上皮细胞进行比较。这个项目 应该能够对非裔美国人前列腺癌特有的体细胞基因变化有明确的见解 癌症及其可能在推动侵袭性疾病和不良后果中所扮演的角色(S) 潜在的其他祖先群体。

Abstract – Project 3 It has long been known that African American men experience a higher incidence and increased mortality from prostate cancer compared to men of other ethnic groups. Socio-economic factors and unequal access to health care undoubtedly contribute to this disparity; however, differences in incidence and outcome remain after considering these factors. This raises the possibility that differences in tumor biology and/or genetic alterations also contribute to the adverse outcomes linked to African American prostate cancer. The over-arching goal of this Project is to comprehensively interrogate the mutational landscape and oncogenic gene expression patterns present in primary African American prostate cancer. Towards this end, we will characterize ~3,000 tumor samples from the RESPOND cohort using whole-exome sequencing and targeted sequencing. Approximately 1,000 of these tumors will also undergo transcriptome analysis. This data will be used to study the relationship between prostate cancer genetics and tumor aggressiveness, and will be compared to cohorts of men of European descent to determine whether any genetic or transcriptional alterations show differential prevalence as a function of ancestry. In addition, we will use in vitro studies of primary prostate epithelial cells to test whether common prostate cancer alterations exert more robust tumorigenic effects when introduced into non-malignant prostate cells from African American men compared to prostate epithelial cells from white men. This project should enable definitive insights into the somatic genetic alterations characteristic of African American prostate cancer and the role(s) they might play in driving aggressive disease and adverse outcomes within this and potentially other ancestral groups.