Cancer Genetics and Epigenetics

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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.