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

Cancer Res. 1999 Jul 1;59(13):3157-65.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, Neoplasm / biosynthesis
  • Antigens, Neoplasm / chemistry
  • Antigens, Neoplasm / genetics*
  • Azacitidine / analogs & derivatives
  • Azacitidine / 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
  • Neoplasm Proteins / chemistry
  • Neoplasm Proteins / genetics*
  • Neoplasms / genetics*
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / chemistry
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Sequence Homology, Nucleic Acid
  • Testis / metabolism*
  • Transcriptional Activation
  • Transfection
  • Tumor Cells, Cultured
  • X Chromosome

Substances

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

Associated data

  • GENBANK/AF055473
  • GENBANK/AF055474
  • GENBANK/AF055475