Targeted expression of MYCN causes neuroblastoma in transgenic mice

William A. Weiss, Ken Aldape, Gayatry Mohapatra, Burt G. Feuerstein, J. Michael Bishop

Research output: Contribution to journalArticle

530 Scopus citations

Abstract

The proto-oncogene MYCN is often amplified in human neuroblastomas. The assumption that the amplification contributes to tumorigenesis has never been tested directly. We have created transgenic mice that over-express MYCN in neuroectodermal cells and develop neuroblastoma. Analysis of tumors by comparative genomic hybridization revealed gains and losses of at least seven chromosomal regions, all of which are syntenic with comparable abnormalities detected in human neuroblastomas. In addition, we have shown that increases in MYCN dosage or deficiencies in either of the tumor suppressor genes NF1 or RB1 can augment tumorigenesis by the transgene. Our results provide direct evidence that MYCN can contribute to the genesis of neuroblastoma, suggest that the genetic events involved in the genesis of neuroblastoma can be tumorigenic in more than one chronological sequence, and offer a model for further study of the pathogenesis and therapy of neuroblastoma.

Original languageEnglish (US)
Pages (from-to)2985-2995
Number of pages11
JournalEMBO Journal
Volume16
Issue number11
DOIs
StatePublished - Jun 2 1997

Keywords

  • Comparative genomic hybridization
  • MYCN
  • N-myc
  • Neuroblastoma
  • Transgenic

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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