[HTML][HTML] Targeted expression of MYCN causes neuroblastoma in transgenic mice

WA Weiss, K Aldape, G Mohapatra… - The EMBO …, 1997 - embopress.org
WA Weiss, K Aldape, G Mohapatra, BG Feuerstein, JM Bishop
The EMBO journal, 1997embopress.org
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 overexpress 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 …
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 overexpress 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.
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