Our observations that every hemangiosarcoma sample tested had wild type sequence for VHL, N-Ras, K-Ras, and H-Ras, no significant elevations of HIF1α, and no constitutive activation of Erk1 and Erk2 suggest that dysregulated VEGF production and the aggressive proliferation seen in these tumors are probably mediated by mechanisms that are independent from abnormalities of VHL and Ras genes. Here, MAPK3 is linked to angiosarcoma.