Project 01: Understanding Racial Disparity in Endometrial Cancer through Tumor Genomics

摘要 子宫内膜癌的发病率每年都在上升，2017年新增病例超过6万例。AS 风险因素在成人和儿童中仍然普遍存在，越来越多的妇女，包括年轻妇女 年龄会发展成子宫内膜癌。研究表明子宫内膜癌存在明显的种族差异 与白人女性相比，黑人女性患有更具侵袭性的疾病，死亡率更高。 虽然造成这种情况的原因是多方面的，但其生物学病因仍有待研究。在这个项目中，我们将 收集来自黑人和白人妇女的子宫内膜肿瘤及其相关临床信息。外显子 将进行测序，并将与临床数据一起进行生物信息学分析，以确定 肿瘤基因组学中的种族差异。此外，尚不清楚黑人女性的肿瘤是否对 黄体酮与白人女性相似。这是拼图中的重要一块，就像年轻的黑人女性一样 与白人女性相比，疾病的严重性更高。子宫内膜肿瘤球体将用于确定 肿瘤的体外孕激素反应和来自外显子组测序的信息，一个预测性信号 将会产生，这在黑人女性中可能会有所不同。最后，孕激素的替代方案 治疗将在体外进行测试，作为孕激素治疗的改进。这项研究将增加我们的 了解子宫内膜癌的种族差异及其对现有孕激素的反应 治疗。我们研究的影响将是重大的，因为我们获得了证据和设计工具来改进 针对黑人和白人妇女子宫内膜癌的个体化孕激素治疗。 好了！

Abstract The incidence of endometrial cancer is on the rise each year reaching over 60,000 new cases for 2017. As risk factors remain prevalent in both adults and children, more and more women including those of younger age will develop endometrial cancer. Studies demonstrate an obvious race disparity in endometrial cancer where black women present with more aggressive disease and a higher death rate compared to white women. While reasons for this are multifactorial, the biological etiology remains to be studied. In this project, we will collect endometrial tumors and its associated clinical information from black and white women. Exome sequencing will be performed and along with clinical data, bioinformatics analysis will be done to determine the racial differences in tumor genomics. In addition, it is unknown whether the tumors in black women respond to progestin similarly to white women. This is an important piece of the puzzle as young black women have increased severity of disease than white women. Endometrial tumor spheroids will be used to determine progestin response of the tumors ex vivo and with information from exome sequencing, a predictive signature will be generated, which may or may not be different in black women. Finally, an alternative to progestin therapy will be tested ex vivo as an improvement to progestin therapy. This research will increase our understanding of racial differences in endometrial cancer and their response to existing progestin treatments. The impact of our studies will be significant, as we obtain evidence and design tools to improve progestin therapy in endometrial cancer in both black and white women in a personalized manner. !