Some PTKs mutations can keep PTKs in a persistently “active” state, causing overactivation of downstream pathways, and everlasting proliferation, differentiation, angiogenesis, and tumorigenesis.1 PTKs overactivation is mediated by four major types of mutations:13 (I) Gain-of-function (GOF) mutations include anaplastic lymphoma receptor tyrosine kinase (ALK), R1275Q, and F1147L mutations in neuroblastoma (NB).14 Some GOF mutations can increase the sensitivity of TKI and signaling transduction. The gene discussed is ALK; the disease is neuroblastoma.