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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.


Journal article


Cancer research

Publication Date





3157 - 3165


Ludwig Institute for Cancer Research, Université Catholique de Louvain, Brussels, Belgium.


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