Oncogenic anaplastic lymphoma kinase (ALK) mutation in neuroblastomas and other pediatric tumors

Neuroblastoma (NB) is one of the most common malignant pediatric tumors that show aggressive behavior. Most advanced-stage NBs have proven refractory to many treatment modalities, and a fundamental alternative therapy, such as inhibition of biological pathways, is now being explored. Anaplastic lymphoma kinase (ALK) has recently been identified as an activation mutation in familial or high-risk sporadic NBs. We examined the prevalence of the ALK mutation in 54 NB cases (23 pre-treatment cases and 31 cases for which specimens were available before and after treatment) and the presence of the ALK mutation in various pediatric tumors. We detected the ALK mutation (F1174C and R1275Q) in 2 (3.7%) of the 54 NB specimens. Both cases showed poorly differentiated and advanced-stage NBs. No ALK mutations were detected in other pediatric tumors. The frequency of the ALK mutation was somewhat lower than that expected in Korean patients with NBs. The mutation detected in the present study was one of the hotspot mutations, including positions of F1174 and R1275 reported previously. The results of the present study suggest the possibility of potential roles of ALK inhibitors in the therapeutics of a small population of neuroblastoma carrying mutated ALK kinases.