In this work, we demonstrate that a recurrent oncoprotein in cancers of the liver, lung, esophagus and other tumors lacks catalytic activity. The MAN2a1-FER fusion gene that includes the catalytic domain of the FER tyrosine kinase lacks some of the invariant amino acids in this type of enzyme, and we demonstrate that the effects attributed to the FER kinase moiety are recovered if a form of FER carrying an inactivating point mutation is expressed. Our results indicate that this oncoprotein cannot therefore be targeted with tyrosine kinase inhibitors, contrary to previous publications.

Desaunay M, Voisset E, Letard S, Roche P, De Sepulveda P. The Recurrent Liver MAN2A1-FER Oncoprotein Lacks Kinase Activity: Implications for the Use of Tyrosine Kinase Inhibitors. Cell Mol Gastroenterol Hepatol. 2024;17(4):667-669.