Cancer Genetics and Epigenetics

项目总结/摘要 埃默里大学温希普癌症研究所的癌症遗传学和表观遗传学（CGE）项目是一个 以实验室为基础的基础科学计划，旨在更好地了解如何改变遗传和表观遗传 基因组的某些组成部分有助于人类癌症的发生和发展。领导下 Paula Vertino博士（领导者）和Jin-Tang Dong博士（共同领导者）的CGE计划包括27个核心项目， 成员来自埃默里大学的14个系和三所学校，包括 医学，埃默里学院和罗林斯公共卫生学院。CGE计划的目标是更好地 了解管理基因组稳定性和适当的基因调控的维持机制 网络，这些网络如何在癌细胞中被破坏，以及它们的破坏如何有助于癌细胞的启动和 癌症的进展。CGE计划旨在促进基因组技术的扩大应用 癌症表型和结果的分子分类。该计划的科学重点是 围绕三个相互关联和互补的主题组织：（1）DNA损伤，修复和细胞 应激反应，（2）表观遗传学和基因调控，（3）癌症遗传学和基因组学。来 上一个竞争周期的CGE计划成员发表了256篇与癌症相关的科学文章。的 其中，55项（21%）是计划内合作，105项（41%）是计划间合作，123项（48%）是计划外合作。 代表与另一个癌症中心或其他学术组织的合作。截至2016年3月31日， CGE每年持有910万美元的癌症相关研究资金，其中约300万美元 (33%）由NCI授予。强大的科学协同作用导致了重要的发现。关键见解 DNA双链断裂修复的机制，复制应激是如何解决的，以及辐射 诱变导致化疗和放射反应的重要预测因子。地标 对泰特双加氧酶的结构和功能的研究已经揭示了氧化的 甲基胞嘧啶残基在5 mC的周转中不仅仅是一个短暂的中间体，而是一个独特的组分 表观遗传“密码”控制基因表达程序。在实现以下目标方面取得了重大进展 该计划的遗传学/基因组学工作的成功翻译，包括新的见解的贡献 关键的“驱动”基因突变和这种改变所揭示的独特的细胞脆弱性，一种基于RNA的 早期检测侵袭性前列腺癌的生物标志物面板，用于风险的联合RNA-DNA测试 口咽癌分层，并实施临床基因组学工作流程，以指导 几种癌症类型的决策。总的来说，CGE计划促进中心范围的目标， 通过识别癌细胞的关键点，改善整个格鲁吉亚州的癌症预后 脆弱性，可以利用新的治疗机会和发展基因组和 表观基因组特征作为临床结果和群体风险的预测因子。

PROJECT SUMMARY/ABSTRACT The Cancer Genetics and Epigenetics (CGE) Program of Winship Cancer Institute of Emory University is a laboratory-based basic science program that seeks to better understand how altered genetic and epigenetic components of the genome contribute to the initiation and progression of human cancers. Under the leadership of Paula Vertino, PhD (leader) and Jin-Tang Dong, PhD (co-leader) the CGE Program includes 27 core members drawn from 14 departments and three schools across Emory University, including the School of Medicine, Emory College, and Rollins School of Public Health. The goals of the CGE program are to better understand the mechanisms that govern the maintenance of genome stability and proper gene regulatory networks, how these become corrupted in cancer cells, and how their disruption contributes to the initiation and progression of cancer. The CGE Program seeks to promote the expanded application of genomic technologies in the molecular classification of cancer phenotypes and outcomes. The scientific focus of the program is organized around three inter-related and complimentary themes: (1) DNA Damage, Repair, and Cellular Responses to Stress, (2) Epigenetics and Gene Regulation, and (3) Cancer Genetics and Genomics. Over the last competitive cycle CGE Program members have published 256 cancer-relevant scientific articles. Of these, 55 (21%) were intra- and 105 (41%) were inter-programmatic collaborations, and 123 (48%) represented a collaboration with another cancer center or other academic organization. As of March 31, 2016, CGE held $9.1 million in annual total cancer-relevant research funding, of which approximately $3 million (33%) was awarded from the NCI. Strong scientific synergism has led to important discoveries. Key insights into the mechanism of DNA double strand break repair, how replication stress is resolved, and radiation mutagenesis are leading to important predictors of chemotherapy and radiation response. Landmark investigations into the structure and function of the TET dioxygenase enzymes have revealed oxidized methylcytosine residues to be more than a transient intermediate in the turnover of 5mC, but a distinct component of the epigenetic ‘code’ governing gene expression programs. Significant strides have been taken towards the successful translation of the program’s genetics/genomics efforts, including new insight into the contribution of key ‘driver’ gene mutations and the unique cellular vulnerabilities that such alterations unmask, an RNA-based biomarker panel for the early detection of aggressive prostate cancer, a combined RNA-DNA test for risk stratification in oropharyngeal carcinomas, and the implementation of a clinical genomics workflow to guide decision making in several cancer types. Overall, the CGE Program promotes center-wide goals for improvements in cancer outcomes across the state of Georgia by identifying of key points of cancer cell vulnerability that can be exploited towards new therapeutic opportunities and the development of genomic and epigenomic signatures as predictors of clinical outcomes and population risk.