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The GAGE-1 gene was identified previously as a gene that codes for an antigenic peptide, YRPRPRRY, which was presented on a human melanoma by HLA-Cw6 molecules and recognized by a clone of CTLs derived from the patient bearing the tumor. By screening a cDNA library from this melanoma, we identified five additional, closely related genes named GAGE-2-6. We report here that further screening of this library led to the identification of two more genes, GAGE-7B and -8. GAGE-1, -2, and -8 code for peptide YRPRPRRY. Using another antitumor CTL clone isolated from the same melanoma patient, we identified antigenic peptide, YYWPRPRRY, which is encoded by GAGE-3, -4, -5, -6, and -7B and which is presented by HLA-A29 molecules. Genomic cloning of GAGE-7B showed that it is composed of five exons. Sequence alignment showed that an additional exon, which is present only in the mRNA of GAGE-1, has been disrupted in gene GAGE-7B by the insertion of a long interspersed repeated element retroposon. These GAGE genes are located in the p11.2-p11.4 region of chromosome X. They are not expressed in normal tissues, except in testis, but a large proportion of tumors of various histological origins express at least one of these genes. Treatment of normal and tumor cultured cells with a demethylating agent, azadeoxycytidine, resulted in the transcriptional activation of GAGE genes, suggesting that their expression in tumors results from a demethylation process.

Type

Journal article

Journal

Cancer Res

Publication Date

01/07/1999

Volume

59

Pages

3157 - 3165

Keywords

Amino Acid Sequence, Animals, Antigens, Neoplasm, Azacitidine, Base Sequence, COS Cells, Chromosome Mapping, Cloning, Molecular, Exons, Gene Expression Regulation, Neoplastic, Gene Library, Humans, Male, Melanoma, Molecular Sequence Data, Multigene Family, Neoplasm Proteins, Neoplasms, Recombinant Proteins, Sequence Alignment, Sequence Homology, Amino Acid, Sequence Homology, Nucleic Acid, Testis, Transcriptional Activation, Transfection, Tumor Cells, Cultured, X Chromosome