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Cancer Genetics Branch, National Human Genome Research Institute [J. K., M. B., Y. C., Y. J., G. C. G., J. M. T., P. S. M.], Biometric Research Branch, National Cancer Institute [R. S.], Biomedical Engineering and Instrumentation Program, National Center for Research Resources [S. B. L., P. D. S.], Computational Bioscience and Engineering Laboratory, Office of Research Services [T. P.], NIH, Bethesda, Maryland 20892
Several forms of human sarcoma, lymphoma, and leukemia are characterized by somatically acquired chromosome translocations that result in fusion genes that encode chimeric transcription factors with oncogenic properties. We have used cDNA microarrays containing 1238 cDNAs to investigate the gene expression profile of a group of seven alveolar rhabdomyosarcoma (ARMS) cell lines characterized by the presence of the PAX3-FKHR fusion gene. Using the method of multidimensional scaling to represent the relationships among the cell lines in two-dimensional Euclidean space, we determined that ARMS cells show a consistent pattern of gene expression, which allows the cells to be clustered together. By searching across the seven ARMS cell lines, we found that 37 of 1238 genes were most consistently expressed in ARMS relative to a reference cell line. Only three of these genes have been previously reported to be expressed in ARMS. Among these 37 were genes related to both primary (PAX3-FKHR) and secondary (CDK4) genetic alterations in ARMS. These results in ARMS demonstrate the potential of cDNA microarray technology to elucidate tumor-specific gene expression profiles in human cancers.
1 Present address: Beecher Instruments, Silver Spring, MD 20910.
2 To whom requests for reprints should be addressed, at National Human Genome Research Institute/NIH, Building 49, Room 4A10, 49 Convent Drive, Bethesda, MD 20892-4470. Phone: (301) 402-2023; Fax: (301) 402-2040; E-mail: pmeltzer@nhgri.nih.gov.
Received 8/ 7/98. Accepted 10/ 1/98.
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T. S. Tanaka, S. A. Jaradat, M. K. Lim, G. J. Kargul, X. Wang, M. J. Grahovac, S. Pantano, Y. Sano, Y. Piao, R. Nagaraja, et al. Genome-wide expression profiling of mid-gestation placenta and embryo using a 15,000 mouse developmental cDNA microarray PNAS, August 1, 2000; 97(16): 9127 - 9132. [Abstract] [Full Text] [PDF] |
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F. Forozan, E. H. Mahlamäki, O. Monni, Y. Chen, R. Veldman, Y. Jiang, G. C. Gooden, S. P. Ethier, A. Kallioniemi, and O.-P. Kallioniemi Comparative Genomic Hybridization Analysis of 38 Breast Cancer Cell Lines: A Basis for Interpreting Complementary DNA Microarray Data Cancer Res., August 1, 2000; 60(16): 4519 - 4525. [Abstract] [Full Text] |
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W. J. Fredericks, K. Ayyanathan, M. Herlyn, J. R. Friedman, and F. J. Rauscher III An Engineered PAX3-KRAB Transcriptional Repressor Inhibits the Malignant Phenotype of Alveolar Rhabdomyosarcoma Cells Harboring the Endogenous PAX3-FKHR Oncogene Mol. Cell. Biol., July 15, 2000; 20(14): 5019 - 5031. [Abstract] [Full Text] |
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A. Wellmann, C. Thieblemont, S. Pittaluga, A. Sakai, E. S. Jaffe, P. Siebert, and M. Raffeld Detection of differentially expressed genes in lymphomas using cDNA arrays: identification of clusterin as a new diagnostic marker for anaplastic large-cell lymphomas Blood, July 15, 2000; 96(2): 398 - 404. [Abstract] [Full Text] [PDF] |
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J. W. Gray and C. Collins Genome changes and gene expression in human solid tumors Carcinogenesis, March 1, 2000; 21(3): 443 - 452. [Abstract] [Full Text] [PDF] |
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M. A. Heiskanen, M. L. Bittner, Y. Chen, J. Khan, K. E. Adler, J. M. Trent, and P. S. Meltzer Detection of Gene Amplification by Genomic Hybridization to cDNA Microarrays Cancer Res., February 1, 2000; 60(4): 799 - 802. [Abstract] [Full Text] |
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S. H Friend How DNA microarrays and expression profiling will affect clinical practice BMJ, November 13, 1999; 319(7220): 1306 - 1306. [Full Text] |
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J. Khan, M. L. Bittner, L. H. Saal, U. Teichmann, D. O. Azorsa, G. C. Gooden, W. J. Pavan, J. M. Trent, and P. S. Meltzer cDNA microarrays detect activation of a myogenic transcription program by the PAX3-FKHR fusion oncogene PNAS, November 9, 1999; 96(23): 13264 - 13269. [Abstract] [Full Text] [PDF] |
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T. R. Golub, D. K. Slonim, P. Tamayo, C. Huard, M. Gaasenbeek, J. P. Mesirov, H. Coller, M. L. Loh, J. R. Downing, M. A. Caligiuri, et al. Molecular Classification of Cancer: Class Discovery and Class Prediction by Gene Expression Monitoring Science, October 15, 1999; 286(5439): 531 - 537. [Abstract] [Full Text] |
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R. Anbazhagan, T. Tihan, D. M. Bornman, J. C. Johnston, J. H. Saltz, A. Weigering, S. Piantadosi, and E. Gabrielson Classification of Small Cell Lung Cancer and Pulmonary Carcinoid by Gene Expression Profiles Cancer Res., October 1, 1999; 59(20): 5119 - 5122. [Abstract] [Full Text] [PDF] |
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A. J. Maniotis, R. Folberg, A. Hess, E. A. Seftor, L. M.G. Gardner, J. Pe'er, J. M. Trent, P. S. Meltzer, and M. J. C. Hendrix Vascular Channel Formation by Human Melanoma Cells in Vivo and in Vitro: Vasculogenic Mimicry Am. J. Pathol., September 1, 1999; 155(3): 739 - 752. [Abstract] [Full Text] [PDF] |
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S. K. Loftus, Y. Chen, G. Gooden, J. F. Ryan, G. Birznieks, M. Hilliard, A. D. Baxevanis, M. Bittner, P. Meltzer, J. Trent, et al. Informatic selection of a neural crest-melanocyte cDNA set for microarray analysis PNAS, August 3, 1999; 96(16): 9277 - 9280. [Abstract] [Full Text] [PDF] |
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K. Ruccione Cancer and Genetics: What We Need to Know Now Journal of Pediatric Oncology Nursing, January 1, 1999; 16(3): 156 - 171. [Abstract] [PDF] |
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C. S. K. Mayanil, D. George, L. Freilich, E. J. Miljan, B. Mania-Farnell, D. G. McLone, and E. G. Bremer Microarray Analysis Detects Novel Pax3 Downstream Target Genes J. Biol. Chem., December 21, 2001; 276(52): 49299 - 49309. [Abstract] [Full Text] [PDF] |
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P. Tang, T. P. Cheng, D. Agnello, C.-Y. Wu, B. D. Hissong, W. T. Watford, H.-J. Ahn, J. Galon, J. Moss, M. Vaughan, et al. Cybr, a cytokine-inducible protein that binds cytohesin-1 and regulates its activity PNAS, March 5, 2002; 99(5): 2625 - 2629. [Abstract] [Full Text] [PDF] |
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O. Monni, M. Barlund, S. Mousses, J. Kononen, G. Sauter, M. Heiskanen, P. Paavola, K. Avela, Y. Chen, M. L. Bittner, et al. Comprehensive copy number and gene expression profiling of the 17q23 amplicon in human breast cancer PNAS, May 8, 2001; 98(10): 5711 - 5716. [Abstract] [Full Text] [PDF] |
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M. West, C. Blanchette, H. Dressman, E. Huang, S. Ishida, R. Spang, H. Zuzan, J. A. Olson Jr., J. R. Marks, and J. R. Nevins Predicting the clinical status of human breast cancer by using gene expression profiles PNAS, September 25, 2001; 98(20): 11462 - 11467. [Abstract] [Full Text] [PDF] |
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L.-L. HSIAO, F. DANGOND, T. YOSHIDA, R. HONG, R. V. JENSEN, J. MISRA, W. DILLON, K. F. LEE, K. E. CLARK, P. HAVERTY, et al. A compendium of gene expression in normal human tissues Physiol Genomics, December 21, 2001; 7(2): 97 - 104. [Abstract] [Full Text] [PDF] |
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