In most RET rearrangements, the transmembrane domain is lost, resulting in a chimeric cytosolic protein that exerts its oncogenic effect through constitutive activation of the kinase domain [161] The majority of RET rearrangements, like ALK and ROS1 fusions, occur in young, non-smoker or mild smoker women with lung adenocarcinoma diagnosis; [173, 177]. Here, RET is linked to lung adenocarcinoma.