Regions syntenic to human 17q are gained in mouse and rat neuroblastoma

M. Lastowska, Y.J. Chung, N.C. Ching, M. Haber, M.D. Norris, Ursula Kees, A.D.J. Pearson, M.S. Jackson

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Abstract

Gain of chromosome arm 17q is the most frequent chromosomal change in human neuroblastoma and is a powerful predictor of adverse outcome of disease. This suggests that the region of gain includes a gene or genes critical for tumor pathogenesis. Analyses of breakpoint positions have revealed that the shortest region of gain (SRG) extends from MPO (17q23.1) to 17qter. Because this encompasses >300 genes, it precludes the identification of candidate genes from human breakpoint data alone. However, mouse chromosome 11, which is syntenic to human chromosome 17, is gained in up to 30% of neuroblastorna tumors developed in a murine MYCN transgenic model of this disease. To confirm that this key genetic change indicates the involvement of a molecular pathway conserved between mouse and man and is not occurring coincidentally in the transgenic model, we used fluorescence in situ hybridization to analyze sporadic cases of both mouse and rat neuroblastoma. Our results confirmed the presence of chromosome 11 gain in all three of the mouse cell lines we analyzed, with the SRG extending from Stat5b (101.6 Mb) to tel. In addition, the rat neuroblastoma cell line harbors an extra copy of distal chromosome 10, extending from 92.8 to 109.3 Mb, which is also syntenic to human 17q. Comparison of the regions gained in all three species has excluded 4.2 Mb from the previously defined region of 17q gain in humans as a likely location of the candidate gene or genes, and strongly suggests that the molecular etiology of neuroblastoma is similar in all three species. (C) 2004 Wiley-Liss, Inc.
Original languageEnglish
Pages (from-to)158-163
JournalGenes, chromosomes & cancer
Volume40
Issue number2
DOIs
Publication statusPublished - 2004

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Lastowska, M., Chung, Y. J., Ching, N. C., Haber, M., Norris, M. D., Kees, U., ... Jackson, M. S. (2004). Regions syntenic to human 17q are gained in mouse and rat neuroblastoma. Genes, chromosomes & cancer, 40(2), 158-163. https://doi.org/10.1002/gcc.20031