R1051Q variant stimulates PI3K/Akt signaling in tumor cells leading to resistance to therapy.153 In melanoma, using SK-MEL-31 cells as a model, R1051Q mutation activated the receptor, stimulating melanoma progression without ligand-binding.154 In the absence of a ligand, VEGFR-2 can form phosphorylated dimers. The gene discussed is PIK3CA; the disease is melanoma.