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[Cancer Research 63, 5266-5273, September 1, 2003]
© 2003 American Association for Cancer Research

Regular Artilces

Genome-wide Array CGH Analysis of Murine Neuroblastoma Reveals Distinct Genomic Aberrations which Parallel those in Human Tumors1 ,, 2

Christopher S. Hackett3, J. Graeme Hodgson2, Mark E. Law, Jane Fridlyand, Kazutoyo Osoegawa, Pieter J. de Jong, Norma J. Nowak, Daniel Pinkel, Donna G. Albertson, Ajay Jain, Robert Jenkins, Joe W. Gray and William A. Weiss4

Departments of Neurology [C. S. H., W. A. W.], Pediatrics [C. S. H., W. A. W.], Neurological Surgery [C. S. H., W. A. W.], Laboratory Medicine [J. G. H., D. P., A. J., J. W. G., W. A. W.], Cancer Center [J. G. H., J. F., D. P., D. G. A., A. J., W. A. W.], and Cancer Research Institute [J. F., D. G. A., A. J., J. W. G.], University of California, San Francisco, California 94143-0114; Department of Laboratory Medicine and Pathology, Mayo Clinic and Foundation, Rochester, Minnesota 55905 [M. E. L., R. J.]; Children’s Hospital Oakland Research Institute, BACPAC Resources, Oakland, California 94609-1809 [K. O., P. J. d. J.]; and Roswell Park Cancer Institute, Buffalo, New York 14263 [N. J. N.]

ABSTRACT

Neuroblastoma, the third most common tumor of childhood, is a complex disease in which few genetic mutations have been identified.Mice expressing a human MYCN oncogene driven by the rat tyrosine hydroxylase promoter (TH-MYCN) represent an animal model for this disorder. We performed microarray-based comparative genomic hybridization analysis on murine tumors, identifying gains on chromosomes 1, 3, 11, 14, 17, and 18 and losses on chromosomes 5, 9, and 16. Fluorescence in situ hybridization analysis confirmed an amplicon on chromosome 18 as the site of TH-MYCN transgene integration. Selected tumors with localized gains of chromosome 11 delineate a 15-Mb region orthologous to human chromosome 17q and help to narrow the minimal region gained in human tumors. We observed clustered loss of chromosomes 5, 9, and 16, orthologous to a similar pattern of combined loss of chromosomes 3p, 4p, and 11q in human tumors. These data demonstrate conservation of many genetic changes in murine and human neuroblastoma and suggest that further delineation of genetic abnormalities in murine tumors may identify genes important in human disease.




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Copyright © 2003 by the American Association for Cancer Research.