This project aims to finding new therapeutic avenues for patients affected by gastrointestinal stromal tumors that lack the classic KIT and PDGFRA mutations.Despite significant advances in the treatment of classic GIST, for which kinase inhibitors such as imatinib have provided a biology-based therapeutic alternative, there is no standard of care for patients with wild-type disease. Collaborative work at the NCI has identified features of these tumors such as lack of succinate dehydrogenase expression and a distinct epigenetic profile.