@article{9e0b5af35b994a869aae099a9ecea254,
title = "Activated ALK Collaborates with MYCN in Neuroblastoma Pathogenesis",
abstract = "Amplification of the MYCN oncogene in childhood neuroblastoma is often accompanied by mutational activation of ALK (anaplastic lymphoma kinase), suggesting their pathogenic cooperation. We generated a transgenic zebrafish model of neuroblastoma in which MYCN-induced tumors arise from a subpopulation of neuroblasts that migrate into the adrenal medulla analog following organogenesis. Coexpression of activated ALK with MYCN in this model triples the disease penetrance and markedly accelerates tumor onset. MYCN overexpression induces adrenal sympathetic neuroblast hyperplasia, blocks chromaffin cell differentiation, and ultimately triggers a developmentally-timed apoptotic response in the hyperplastic sympathoadrenal cells. Coexpression of activated ALK with MYCN provides prosurvival signals that block this apoptotic response and allow continued expansion and oncogenic transformation of hyperplastic neuroblasts, thus promoting progression to neuroblastoma.",
author = "Shizhen Zhu and Lee, {Jeong Soo} and Feng Guo and Jimann Shin and Perez-Atayde, {Antonio R.} and Kutok, {Jeffery L.} and Rodig, {Scott J.} and Neuberg, {Donna S.} and Daniel Helman and Hui Feng and Stewart, {Rodney A.} and Wenchao Wang and George, {Rani E.} and Kanki, {John P.} and Look, {A. Thomas}",
note = "Funding Information: This work was supported by a grant CA104605 from the National Cancer Institute, NIH (A.T.L.), a Young Investigator Award from Children's Tumor Foundation and Neuroblastoma Foundation (J.S.L.), a fellowship from the Friends for Life (S.Z., R.E.G.), a fellowship from the Hope Street Kids Foundation (J.S.L.), a fellowship from Durand Family Fund for Pediatric Neuroblastoma Research (J.S.L.), a fellowship from the David A. Abraham Fund and Pediatric Low Grade Astrocytoma Foundation (J.S.), an award K99CA134743 from the National Cancer Institute, NIH (H.F.), an award R00 NS058608 from NIH/NINDS (R.A.S.), and a grant from the National Institutes of Health and the Children's Oncology Group (R.E.G.). We thank John Gilbert for editing the manuscript and critical comments, and Greg Molind, Lu Zhang, Derek Walsh, and John P. Lyons for excellent care of our zebrafish facility. ",
year = "2012",
month = mar,
day = "20",
doi = "10.1016/j.ccr.2012.02.010",
language = "English (US)",
volume = "21",
pages = "362--373",
journal = "Cancer cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "3",
}