Abstract
Abstract Neuroblastoma is the most common extracranial solid tumor in children and originates during development of the peripheral sympathetic nervous system. Advanced-stage disease and a poor outcome are associated with amplification of the MYCN oncogene, often in combination with mutational activation or amplification of another oncogene ALK (anaplastic lymphoma kinase), suggesting that they cooperate in neuroblastoma pathogenesis. To investigate this possibility, we generated a transgenic zebrafish model of neuroblastoma in which human MYCN is expressed under the control of the dopamine-beta-hydroxylase promoter, and show that the resultant tumors recapitulate childhood neuroblastomas histologically, immunohistochemically, and ultrastructurally. Surprisingly, the tumors arise from a subpopulation of neuroblasts that migrate into the adrenal analogue (interrenal gland) in the zebrafish after organogenesis is complete. Coexpression of activated ALK with MYCN markedly increased the frequency of neuroblastoma and accelerated the time of onset, providing conclusive evidence for synergistic interplay between these two oncogenes in neuroblastoma pathogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4296. doi:10.1158/1538-7445.AM2011-4296
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call