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[Cancer Research 65, 9226-9235, October 15, 2005]
© 2005 American Association for Cancer Research

Molecular Biology, Pathobiology and Genetics

Gene Expression Profiling of Human Sarcomas: Insights into Sarcoma Biology

Kristin Baird1, Sean Davis1, Cristina R. Antonescu3, Ursula L. Harper1, Robert L. Walker1, Yidong Chen1, Arthur A. Glatfelter1, Paul H. Duray2 and Paul S. Meltzer1

1 Cancer Genetics Branch, National Human Genome Research Institute; 2 Laboratory of Pathology, National Cancer Institute, NIH, Bethesda, Maryland; 3 Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York

Requests for reprints: Paul S. Meltzer, National Human Genome Research Institute, NIH, 50 South Drive, Bethesda, MD 20892-8000. Phone: 301-594-5283; Fax: 301-402-3281; E-mail: pmeltzer{at}mail.nih.gov.

Sarcomas are a biologically complex group of tumors of mesenchymal origin. By using gene expression microarray analysis, we aimed to find clues into the cellular differentiation and oncogenic pathways active in these tumors as well as potential biomarkers and therapeutic targets. We examined 181 tumors representing 16 classes of human bone and soft tissue sarcomas on a 12,601-feature cDNA microarray. Remarkably, 2,766 probes differentially expressed across this sample set clearly delineated the various tumor classes. Several genes of potential biological and therapeutic interest were associated with each sarcoma type, including specific tyrosine kinases, transcription factors, and homeobox genes. We also identified subgroups of tumors within the liposarcomas, leiomyosarcomas, and malignant fibrous histiocytomas. We found significant gene ontology correlates for each tumor group and identified similarity to normal tissues by Gene Set Enrichment Analysis. Mutation analysis done on 275 tumor samples revealed that the high expression of epidermal growth factor receptor (EGFR) in certain tumors was not associated with gene mutations. Finally, to further the investigation of human sarcoma biology, we have created an online, publicly available, searchable database housing the data from the gene expression profiles of these tumors (http://watson.nhgri.nih.gov/sarcoma), allowing the user to interactively explore this data set in depth.




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Copyright © 2005 by the American Association for Cancer Research.