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Identification of a Novel Gene, GASC1, within an Amplicon at 9p23–24 Frequently Detected in Esophageal Cancer Cell Lines¹

Department of Molecular Cytogenetics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113-8519, Japan [Z-Q. Y., I. M., Y. F., A. P., J. I.]; Department of Surgery and Surgical Basic Science, Kyoto University Graduate School of Medicine, Kyoto, Japan [Y. S., M. I.]; and Department of Virology [S. S.] and Laboratory of Genome Medicine [Y. N.], Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan

In a recent study, we identified frequent amplification of DNA copy number at chromosome 9p23–24 in cell lines derived from esophageal squamous cell carcinomas (ESCs), using comparative genomic hybridization. Because amplified regions often harbor oncogenes and/or other tumor-associated genes, and because 9p23–24 amplification had been reported in various other types of cancers, we used fluorescence in situ hybridization and Southern blot analysis to map the 9p23–24 amplicon. We then screened target genes/transcripts present within this amplicon by Northern blotting. With this strategy, we successfully cloned a novel gene, designated gene amplified in squamous cell carcinoma 1 (GASC1), that was amplified and overexpressed in several ESC cell lines. The deduced amino acid sequence of GASC1 contains two PHD-finger motifs and a PX domain. PHD-finger motifs are found in nuclear proteins that participate in chromatin-mediated transcriptional regulation and are present in a number of proto-oncogenes. Our findings suggest that overexpressed GASC1 may play an important role in the development and/or progression of various types of cancer including ESC.

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