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(American Journal of Pathology. 2002;161:1315-1323.)
© 2002 American Society for Investigative Pathology

Regular Articles

Large Scale Molecular Analysis Identifies Genes with Altered Expression in Salivary Adenoid Cystic Carcinoma

Henry F. Frierson, Jr*, Adel K. El-Naggar{dagger}, John B. Welsh{ddagger}, Lisa M. Sapinoso{ddagger}, Andrew I. Su§, Jun Cheng, Takashi Saku, Christopher A. Moskaluk* and Garret M. Hampton{ddagger}

From the Department of Pathology,* University of Virginia Health System, Charlottesville, Virginia; the Department of Pathology,{dagger} University of Texas M.D. Anderson Cancer Center, Houston, Texas; the Genomics Institute of the Novartis Research Foundation,{ddagger} San Diego, California; The Scripps Research Institute,§ La Jolla, California; and the Department of Tissue Regeneration and Reconstruction, Division of Oral Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan

Correspondence: Address correspondence to Henry F. Frierson, Jr., M.D., Department of Pathology, P.O. Box 800214, University of Virginia Health System, Charlottesville, VA 22908-0214. E-mail: hff{at}virginia.edu

Salivary gland cancers comprise a heterogeneous group of neoplasms whose biological and clinical characteristics differ considerably from those of mucosal squamous cell carcinomas of the head and neck. One of the most common subtypes, adenoid cystic carcinoma (ACC), is notable for its myoepithelial differentiation, proclivity for hematogenous spread, and slow but progressive clinical course. The molecular alterations that underlie its development and progression are poorly characterized. Here we used oligonucleotide microarray analysis to survey the expression of 8920 different human genes in 15 ACCs, one ACC cell line, and five normal major salivary glands. We observed expression of genes indicative of myoepithelial differentiation, as expected, including those whose protein products are components of basement membranes and extracellular matrix. Other genes that were highly ranked for their expression in ACC were those encoding the transcription factors SOX4 and AP-2{gamma}, the latter of which also was overexpressed in ACC relative to 175 other carcinomas from 10 anatomical sites that we had previously profiled. Additional genes, which were highly expressed in ACC compared to the other carcinomas, included casein kinase 1, epsilon and frizzled-7, both members of the Wnt/ß-catenin signaling pathway. Our study documents for the first time the diverse spectrum of genes overexpressed in ACC and highlights gene products and pathways that in the future might be exploited as therapeutic targets for this cancer, which up until now, has shown limited response to chemotherapeutic approaches.




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