SPRED2 and melanoma: Of note, also in our study upregulation/gain of FGFR1 (together with FGF1), loss of negative MAPK regulators including SPRY1, SPRY2 and SPRED2, and deregulation of multiple small GTPases including Rab- and Rap-regulators were associated, in addition to PTEN loss, with a more aggressive melanoma phenotype.