PLCG1 and angiosarcoma: Endothelial cells secrete PDGF-BB, which increases pericyte coverage and maintains the integrity of the endothelial cell basement membrane.54 At least five different PDGF isoforms interact with two different PDGF receptors (PDGFRs).55 PDGFR activation results in autophosphorylation of the receptor, which in turn activates phospholipase C-gamma (PLCG).56 As described below, PLCG1 activation by VEGFR2 acts as a driver for a subset of angiosarcomas and leads to resistance to VEGF/VEGFR targeted therapies.