Characterization of the GAGE genes that are expressed in various human cancers and in normal testis.

Abstract

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.

• Authors: O De Backer, K C Arden, M Boretti, V Vantomme, C De Smet, S Czekay, C S Viars, E De Plaen, F Brasseur, P Chomez, B Van den Eynde, T Boon, P van der Bruggen
• Journal: Cancer research (Cancer Res) Vol. 59 Issue 13 Pg. 3157-65 (Jul 01 1999) ISSN: 0008-5472 [Print] United States
• PMID: 10397259 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• Neoplasm Proteins
• Recombinant Proteins
• Decitabine
• Azacitidine

Topics

• Amino Acid Sequence
• Animals
• Antigens, Neoplasm (biosynthesis, chemistry, genetics)
• Azacitidine (analogs & derivatives, pharmacology)
• Base Sequence
• COS Cells
• Chromosome Mapping
• Cloning, Molecular
• Decitabine
• Exons
• Gene Expression Regulation, Neoplastic (drug effects)
• Gene Library
• Humans
• Male
• Melanoma (genetics)
• Molecular Sequence Data
• Multigene Family
• Neoplasm Proteins (biosynthesis, chemistry, genetics)
• Neoplasms (genetics)
• Recombinant Proteins (biosynthesis, chemistry)
• Sequence Alignment
• Sequence Homology, Amino Acid
• Sequence Homology, Nucleic Acid
• Testis (metabolism)
• Transcriptional Activation
• Transfection
• Tumor Cells, Cultured
• X Chromosome