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[Cancer Research 58, 5009-5013, November 15, 1998]
© 1998 American Association for Cancer Research

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Gene Expression Profiling of Alveolar Rhabdomyosarcoma with cDNA Microarrays

Javed Khan, Richard Simon, Michael Bittner, Yidong Chen, Stephen B. Leighton1, Thomas Pohida, Paul D. Smith, Yuan Jiang, Gerald C. Gooden, Jeffrey M. Trent and Paul S. Meltzer2

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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Helicobacter pylori infection induced alteration of gene expression in human gastric cells
Gut, May 1, 2001; 48(5): 598 - 604.
[Abstract] [Full Text] [PDF]


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Cancer Res.Home page
C. Khanna, J. Khan, P. Nguyen, J. Prehn, J. Caylor, C. Yeung, J. Trepel, P. Meltzer, and L. Helman
Metastasis-associated Differences in Gene Expression in a Murine Model of Osteosarcoma
Cancer Res., May 1, 2001; 61(9): 3750 - 3759.
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NEJMHome page
I. Hedenfalk, D. Duggan, Y. Chen, M. Radmacher, M. Bittner, R. Simon, P. Meltzer, B. Gusterson, M. Esteller, M. Raffeld, et al.
Gene-Expression Profiles in Hereditary Breast Cancer
N. Engl. J. Med., February 22, 2001; 344(8): 539 - 548.
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INT J SURG PATHOLHome page
E. de Alava and J. Pardo
Ewing Tumor: Tumor Biology and Clinical Applications
International Journal of Surgical Pathology, January 1, 2001; 9(1): 7 - 17.
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Hum Mol GenetHome page
F. Bertucci, R. Houlgatte, A. Benziane, S. Granjeaud, J. Adelaide, R. Tagett, B. Loriod, J. Jacquemier, P. Viens, B. Jordan, et al.
Gene expression profiling of primary breast carcinomas using arrays of candidate genes
Hum. Mol. Genet., December 1, 2000; 9(20): 2981 - 2991.
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Cancer Res.Home page
S.-L. Sallinen, P. K. Sallinen, H. K. Haapasalo, H. J. Helin, P. T. Helén, P. Schraml, O.-P. Kallioniemi, and J. Kononen
Identification of Differentially Expressed Genes in Human Gliomas by DNA Microarray and Tissue Chip Techniques
Cancer Res., December 1, 2000; 60(23): 6617 - 6622.
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Physiol. GenomicsHome page
B. K. DIECKGRAEFE, W. F. STENSON, J. R. KORZENIK, P. E. SWANSON, and C. A. HARRINGTON
Analysis of mucosal gene expression in inflammatory bowel disease by parallel oligonucleotide arrays
Physiol Genomics, November 9, 2000; 4(1): 1 - 11.
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Cancer Res.Home page
Q. M. Guo, R. L. Malek, S. Kim, C. Chiao, M. He, M. Ruffy, K. Sanka, N. H. Lee, C. V. Dang, and E. T. Liu
Identification of c-Myc Responsive Genes Using Rat cDNA Microarray
Cancer Res., November 1, 2000; 60(21): 5922 - 5928.
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Cancer Res.Home page
P. Kauraniemi, I. Hedenfalk, K. Persson, D. J. Duggan, M. Tanner, O. Johannsson, H. Olsson, J. M. Trent, J. Isola, and A. Borg
MYB Oncogene Amplification in Hereditary BRCA1 Breast Cancer
Cancer Res., October 1, 2000; 60(19): 5323 - 5328.
[Abstract] [Full Text]


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JNCI J Natl Cancer InstHome page
M. Barlund, F. Forozan, J. Kononen, L. Bubendorf, Y. Chen, M. L. Bittner, J. Torhorst, P. Haas, C. Bucher, G. Sauter, et al.
Detecting Activation of Ribosomal Protein S6 Kinase by Complementary DNA and Tissue Microarray Analysis
J Natl Cancer Inst, August 2, 2000; 92(15): 1252 - 1259.
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Proc. Natl. Acad. Sci. USAHome page
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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Cancer Res.Home page
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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Mol. Cell. Biol.Home page
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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BloodHome page
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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CarcinogenesisHome page
J. W. Gray and C. Collins
Genome changes and gene expression in human solid tumors
Carcinogenesis, March 1, 2000; 21(3): 443 - 452.
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Cancer Res.Home page
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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BMJHome page
S. H Friend
How DNA microarrays and expression profiling will affect clinical practice
BMJ, November 13, 1999; 319(7220): 1306 - 1306.
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Proc. Natl. Acad. Sci. USAHome page
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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ScienceHome page
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.
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Cancer Res.Home page
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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Am. J. Pathol.Home page
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.
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Proc. Natl. Acad. Sci. USAHome page
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.
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Journal of Pediatric Oncology NursingHome page
K. Ruccione
Cancer and Genetics: What We Need to Know Now
Journal of Pediatric Oncology Nursing, January 1, 1999; 16(3): 156 - 171.
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J. Biol. Chem.Home page
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.
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Proc. Natl. Acad. Sci. USAHome page
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.
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Proc. Natl. Acad. Sci. USAHome page
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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Proc. Natl. Acad. Sci. USAHome page
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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Physiol. GenomicsHome page
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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