MYCN and mutationally activated ALK synergise in neuroblastoma

Childhood neuroblastoma, a neuroendocrine tumour of the peripheral sympathetic nervous system, is associated with amplification of the MYCN oncogene and mutational activation of ALK (encoding anaplastic lymphoma kinase). Models that clarify whether and how these genes interact in the development of neuroblastoma are limited. Zhu et al. generated transgenic zebrafish overexpressing human MYCN and activated ALK, resulting in tumours that closely mimic those observed in the human disease. The authors show that MYCN over-expression alone causes aberrant neuroblast hyperplasia early during development, which is offset in part by a subsequent apoptotic event; surviving MYCN-over-expressing cells fail to differentiate and give rise to neuroblastoma. Co-expression of mutationally activated ALK blocks the apoptotic event but does not restore neuroblast differentiation, tripling penetrance and accelerating the onset of neuroblastoma. These results provide insight into the synergistic relationship between two important mediators of neuroblastoma, and could help in developing treatments for the disease.