Although neither germ-line nor somatic mutations in Notch4 have been systematically explored in NSCLC, a P1663Q mutation (Table 1) in the ankyrin repeat (ANK) region of the receptor (preliminarily predicted to act as an oncogenic, gain-of-function alteration) has been identified in Hispanic ACL patients [108], and, furthermore, a homogeneous (presumably non-somatic) mutation has been reported in malignant pulmonary granular cell tumor [109]. The gene discussed is NOTCH4; the disease is non-small cell lung carcinoma.