Targeted expression of MYCN causes neuroblastoma in transgenic mice.
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.
Weiss
W A
WA
G.W. Hooper Foundation, and Department of Neurology, University of California, San Francisco 94143-0552, USA.
Aldape
K
K
Mohapatra
G
G
Feuerstein
B G
BG
Bishop
J M
JM
D000005:Abdomen / Q000473:pathology; D000818:Animals; D002869:Chromosome Aberrations; D025063:Chromosome Disorders; D004273:DNA, Neoplasm / Q000235:genetics; D018628:Gene Dosage; D015870:Gene Expression; D018390:Gene Targeting; D016259:Genes, myc; D051379:Mice; D008822:Mice, Transgenic; D009362:Neoplasm Metastasis; D009447:Neuroblastoma / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D017599:Neuroectodermal Tumors / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D009693:Nucleic Acid Hybridization; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis*; D013045:Species Specificity; D013909:Thorax / Q000473:pathology
D004273:DNA, Neoplasm; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc