PROJECT SUMMARY/ABSTRACT (CANCER GENETICS) The University of Michigan (U-M) Rogel Cancer Center (Rogel) Cancer Genetics (CG) Program is a group of interdisciplinary researchers who seek to advance knowledge of the genetic and epigenetic mechanisms that underlie cancer development and progression. Investigators in the CG Program perform basic and translational research aimed at understanding the origins and nature of cancer, thereby leading to novel preventive and diagnostic approaches as well as the improved clinical management of cancer patients. To reach these goals, the CG Program is organized as a diverse, interdisciplinary research group with 42 members from 18 departments within four U-M schools/colleges (i.e., Medical School; School of Public Health, School of Kinesiology, College of Literature, Science and the Arts). Currently, annual direct research support totals $11.6M in cancer grant funding with $3.2M (28%) from NCI, $3.6M (31%) from other NIH grants, and $2.1M (18%) from additional peer-reviewed funding. CG members are actively involved in intra- and inter-programmatic interactions with researchers in the Basic Science, Clinical Research, and Cancer Control and Population Sciences Programs. The work being done by CG members is particularly relevant to five of the Rogel’s cross-cutting research themes, specifically i) molecular determinants of cancer; ii) biomarkers; iii) genetics and gene environment, iv) targets and therapeutics and v) inflammation, microbes, and immunity. With combined effort, the Program has generated important insights in cancer development, diagnosis, treatment, and prevention, having authored a total of almost 700 cancer-relevant publications during the project period, of which 18.7% were intra-programmatic and 46% were inter-programmatic. In the current proposal, three scientific aims are detailed: 1) Elucidate the genetic and epigenetic mechanisms of cancer development and progression, 2) Utilize novel animal model systems for characterizing the impact of critical genetic alterations found in human cancers, and 3) Generate new knowledge for translation into effective strategies for prevention, early diagnosis, and treatment. By focusing efforts on shared scientific interest across Rogel programs, in tandem with a commitment to training as well as mentorship, CG Program members have generated a cohesive body of knowledge that has yielded novel and important insights into the genetic and epigenetic mechanisms underlying cancer initiation and progression. In keeping with these accomplishments, the Program seeks to further advance the development of new strategies for preventing, diagnosing, and treating cancer.