RHOA drivers take alternate routes in gastric cancer

Oncogenic small guanosine triphosphatases (GTPases) are often characterized by a limited set of activating mutations that affect their intrinsic biochemical function, but RHOA—which is frequently mutated in gastric cancer—appears not to have read the instruction manual. Having previously characterized the Y42C RHOA mutation in gastric cancer, in this issue of Science Signaling , Schaefer et al. take on the slightly less common L57V mutation and find that individual RHOA mutations can have different and unpredictable signaling outcomes.