The Vermont Cancer Center (VCC), in Burlington, Vermont, is a matrix- based cancer center located on the campus of the University of Vermont. It is closely tied to the University of Vermont College of Medicine. Since its founding in 1974, the Vermont Cancer Center has been committed to its mission in research, education and service to the people of the Vermont and their neighbors in northern New York. Although it is the smallest NCI-designated Comprehensive Cancer Center, its central role in the UVM College of Medicine and the unusual nature of the rural and relatively stable population it serves have created an ideal environment for integration of basic, clinical and population-directed research related to cancer. After a period of aggressive reorganization within the Institution and within the Cancer Center it self, this CCSG renewal application reflects the diverse strengths of the Center in a substantially changed organizational and programmatic format. Four Research Programs are presented. Two are strongly grounded in basic research (1-Genome Stability and Expression Research Program; 2-Cell Signalling and Growth Control Research Program) but have clear links to cancer as a disease through studies at the 1) molecular/mechanistic, or 2) the cellular/biological level. A reorganized Clinical Research Program has a strong clinical/translation focus with both laboratory- and clinic-based research studies. Finally, the Center's Cancer Prevention and Control Research Program focuses on problems of major significance in the region served by the Center and includes a new emphasis on population-based studies of familial cancer predisposition. Seven Shared Resources or Support Services are presented, including two that are new to the Center and several that have been reorganized. These include: Biostatistics and Biometry Shared Resource, Bioanalytical Shared Resource, DNA Analysis Shared Resource, Cell Imaging Facility Shared Resource, Molecular Modeling Shared Resource, the Clinical Research Management shared Resource, and the Clinical Research Protocol Support Service. Developmental funds for pilot studies and recruitment of investigators critical to the Center's research mission are also requested.