PROJECT SUMMARY/ABSTRACT (CANCER GENETICS) The 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 35 members from 19 departments within three U-M schools/colleges (i.e., Medical School; School of Public Health, College of Literature, Science and the Arts). Currently, annual direct research support totals $11.1M in cancer grant funding with $3.5M (31%) from NCI, $3.9M (35%) from other NIH grants, and $2.6M (24%) 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. Members focus their efforts on one or more of four interrelated themes, including oncogene and tumor suppressor gene networks, transcription factor/chromatin modification complexes, genomic instability, and the development of clinically relevant, genetically-engineered animal models. 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 14% were intra-programmatic and 52% 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 key genetic alterations found in human cancers, and 3) advance approaches for translating new insights into effective strategies for cancer prevention, early diagnosis, and treatment. By focusing efforts on shared scientific interest across UMCCC 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.!