|Tumor Type||Primary Site|
The anaplastic lymphoma kinase (ALK) has emerged as a potentially relevant biomarker and therapeutic target in pediatric solid and hematologic malignancies. It is a receptor tyrosine kinase (RTK) that is known to be activated either by point mutations or by chromosomal translocations. These genetic alterations act as oncogenic drivers and promote constitutive, ligand-independent activation of this RTK. Recurrent activating point mutations are seen within kinase domain in both the hereditary and sporadic form of neuroblastoma cases (7-10%). According to some studies, the presence of an ALK aberration could be a biomarker of aggressive disease and inferior clinical outcome. Clinical trials of crizotinib in neuroblastoma are underway. The R1275Q mutation is most common variant among ALK-mutated neuroblastomas (33%), and is found in both sporadic and familial cases. The R1275 amino acid substitution lies within the activation loop and causes constitutive ligand-independent activation of this RTK. Both preclinical and clinical studies suggest that this mutation could be sensitive to ALK inhibition.