This application represents unprecedented cooperation among excellent institutions, major sarcoma dedicated non-profit organizations, and the NCI intramural Program. This SPORE originates from SARC, a non-for-profit consortium that facilitates the conduct of research among national centers of excellence in sarcoma. The main goals of the SARC Sarcoma SPORE are the translation of biological and technological advances into improvements in prevention, diagnostics, predictors of outcome, and - particularly - advances in the treatment of sarcoma. The SARC Sarcoma SPORE is anchored by multiple researchers from SARC, Harvard, MD Anderson Cancer Center, and the NCI intramural program, but also includes key individual researchers from Stanford University, Columbia University and The University of Michigan. The researchers represent medical and pediatric oncology and the projects explore both soft tissue and bone sarcomas. Four major projects are proposed: 1) HDACi-based therapeutic strategies for the treatment of genetically complex STS; 2) Identification of therapeutic windows for NFI-related malignant peripheral nerve sheath tumor; 3) Investigation of G-protein coupled receptors as biomarkers of aggressive disease and novel therapeutic targets in Ewing sarcoma; and 4) Development of quantitative imaging biomarkers for assessing therapeutic response to sarcoma therapy using advanced approaches in PET and MRl. These projects are integrated and supported by 4 cores: 1) Administration, Evaluation and Planning; 2) Tissue and Pathology; 3) Clinical Trials; and 4) Biostatistics. The SPORE application outlines a Developmental Research Program that includes a plan for selection of new projects as well as 14 proposed developmental pilot projects. We also include a Career Developmental Program that outlines a mechanism for the identification and support of talented young investigators in translational or clinical sarcoma research. The projects, cores and programs are highly integrated and are poised to take maximum advantage of the SPORE mechanism to achieve translational goals. This SPORE joins state-of-the-art research projects with the multi-institution, collaborative strength of SARC and commitments from leading institutions to produce translational advances.