ABSTRACT The Sidney Kimmel Comprehensive Cancer Center (SKCCC) Cancer Genetics and Epigenetics (CGE) Program's overall goal is to enhance understanding of the initiation and progression of cancer at a cellular and molecular biology level. Findings are translated through trials within the Program and, more often, by contributing concepts to clinical trials and biomarker efforts in collaboration with other SKCCC Programs. The SKCCC prioritizes the definition of the genetic and epigenetic alterations that drive individual human cancers in order to develop personalized cancer care. To implement its aims, CGE Program Leadership and Membership are integrated into virtually all activities in the SKCCC, including key administrative activities, collaborative work with virtually all of the SKCCC Programs, and utilization and management of SKCCC Shared Resources. The Program consists of 38 Program full Members, 31 of whom have peer-reviewed funding, and an additional two Associate Members, including one with an active K awards during this last funding period. The Program has members with appointments in nine departments across two schools at Johns Hopkins. The total direct cancer- relevant peer-reviewed funding for the Program is $11.3 million, with $7.7 million from the National Cancer Institute. The total number of publications by Program members since last review is 807, of which 197 (24.4%) are Intra-Programmatic, 383 (47.5%) are Inter-Programmatic and 616 (76.3%) have external collaborations. Of these publications, 23.4% are in journals with impact factors >10 and 8.8% in journals with impact factors >25. Under the direction of Nilofer Azad, M.D.; Stephen Baylin, M.D.; and Victor Velculescu, M.D., Ph.D., the Specific Aims of the CGE Program are: Aim 1: To define genetic abnormalities that drive human cancer initiation and progression, particularly those that may be amenable to therapeutic or diagnostic intervention. Aim 2: To characterize the molecular and epigenetic changes that underlie tumor initiation and progression, and harness this information to design therapeutic strategies and devise biomarker approaches. Aim 3: To translate basic findings to preclinical studies to provide concepts for clinical investigator-initiated trials led by CGE Program Members and other SKCCC Program Members. These aims enrich the translational goals of the SKCCC, particularly in designing new therapy paradigms for many common types of human malignancies and deriving molecularly based biomarker strategies for early cancer detection, prognostic prediction and monitoring cancer progression.