For example, in WT GIST, an IGF2-IGF1R autocrine/paracrine loop sustained by overexpression of both the receptor and its ligand in the same tumor microenvironment [5,16,17,57,58] may activate a secondary autocrine/paracrine loop formed by KITLG and WT KIT leading to increased KIT phosphorylation (refs. 9,10,13 and present results) and cell proliferation. The gene discussed is IGF2; the disease is neoplasm.