Alteration of Alk in Neuroblastoma

Jeon, In Sang

Abstract

Neuroblastoma, one of the common pediatric solid tumor, shows variable clinical outcome depending on the prognostic factors. Several molecular changes including N-myc amplification have been elucidated as one of the prognostic factor. However, their role in the pathogenesis of neuroblastoma is still not clearly documented. Recently, an alteration of Alk, a tyrosine kinase receptor gene preferentially expressed in the central and peripheral nervous systems, was observed in neuroblastoma. Germ line and somatic Alk amplification were found around 25% of familial and sporadic cases of neuroblastoma. In addition, about 20 types of activating Alk mutations were reported, too. Most of the mutations were missense mutation and localized within the tyrosine kinase domain of the Alk. The most common types of mutation were F1174L and R1275Q, which occupying about 60% of total cases. These alterations were mainly observed in the advanced cases of neuroblastoma or with N-myc amplification. This observable fact suggests that the Alk alteration could be used as an prognostic factor of neuroblastoma. It is interesting that the neuroblastoma is related to the activating Alk-driven pathway. Moreover, the understanding of the molecular oncogenesis of the neuroblastoma would be advanced through the study of the altered tyrosine kinase receptor gene, Alk. Besides, this finding could be applied to inhibit Alk signaling as an effective molecular therapy of neuroblastoma.