Endogenous expression of the R-RAS2 GTPase carrying the Q72L hotspot mutation is relevant for the tumorigenic phenotype of cancer cells

The R-RAS2 GTPase has been considered quite similar to classical RAS proteins at the regulatory, signaling, and functional level. The interest in this GTPase has been reinvigorated upon the recent discovery that a long-tail hotspot RRAS2 mutation found in human tumors (Gln72 to Leu) can act as a potent oncogenic driver. Here, we report that the Q72L mutation and other gain-of-function mutations of RRAS2 play roles in tumor initiation and maintenance. Such roles are unlikely to be redundant to those normally executed by classical RAS proteins. Control and R-RAS2Q72L-knockout A2780 cells