MYCN promotes the expansion of Phox2B-positive neuronal progenitors to drive neuroblastoma development

Goleeta Alam, Hongjuan Cui, Huilin Shi, Liqun Yang, Jane Ding, Ling Mao, William A. Maltese, Han Fei Ding

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54 Scopus citations

Abstract

Amplification of the oncogene MYCN is a tumorigenic event in the development of a subset of neuroblastomas that commonly consist of undifferentiated or poorly differentiated neuroblasts with unfavorable clinical outcome. The cellular origin of these neuroblasts is unknown. Additionally, the cellular functions and target cells of MYCN in neuroblastoma development remain undefined. Here we examine the cell types that drive neuroblastoma development in TH-MYCN transgenic mice, an animal model of the human disease. Neuroblastoma development in these mice begins with hyperplastic lesions in early post-natal sympathetic ganglia. We show that both hyperplasia and primary tumors are composed predominantly of highly proliferative Phox2B+ neuronal progenitors. MYCN induces the expansion of these progenitors by both promoting their proliferation and preventing their differentiation. We further identify a minor population of undifferentiated nestin+ cells in both hyperplastic lesions and primary tumors that may serve as precursors of Phox2B+ neuronal progenitors. These findings establish the identity of neuroblasts that characterize the tumor phenotype and suggest a cellular pathway by which MYCN can promote neuroblastoma development.

Original languageEnglish (US)
Pages (from-to)856-866
Number of pages11
JournalAmerican Journal of Pathology
Volume175
Issue number2
DOIs
StatePublished - Aug 2009

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ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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