Hage et sage : deux nouveaux gènes exprimés préférentiellement dans les tumeurs

Martelange, Valérie
(2001)

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Authors
  • Martelange, ValérieUCLouvain
    author
Supervisors
De Plaen, Etienne
;
Boon, Thierry
Abstract
Genes MAGE, BAGE, GAGE and LAGE/NY-ESO-1 encode surface antigens that are recognized on tumor cells by autologous cytolytic T lymphocytes. Since these genes are expressed in a significant proportion of tumors from various histological types but nor in normal tissues, the antigens they encode may serve as targets for cancer immunotherapy. Clinical trials are going on melanoma patients and the results, although preliminary, are rather encouraging. <BR> In order to identify new genes presenting the same pattern of expression as the MAGE-type genes, i.e. expressed in tumors but not in normal tissues except testis, we applied the Representational Difference Analysis method, that couples subtractive hybridization and PCR amplification of cDNA. <BR> We have performed a testis cDNA enrichment in order to test whether genes expressed in testis were also activated in tumors. We observed that most of the cDNA fragments that we obtained were derived from gene expressed only or preferentially in testis. Those genes were not activated in tumors. This suggests that the MAGE-type genes belong to a minor subset of testis-specific genes that are expressed in tumors of various types. <BR> We have also enriched cDNA from the sarcoma cell line. LB23-SAR. This allowed us to identify three genes presenting an interesting pattern of expression. Gene SAR35 is highly expressed in a high percentage of tumors from various histological types but the expression of this gene in some normal tissues may prevent its use in immunotherapy. On the other hand, genes SAGE and HAGE present a pattern of expression similar to that of MAGE-type genes: they are not expressed in normal tissues except testis and they are activated in tumors. Because of this tumor-specific expression, genes SAGE en HAGE ought to encode antigens that could be useful for anti-tumoral therapeutic vaccination. The function of these three genes is unknown. However preliminary results and the features common to the protein encoded by gen SAR35 and protein HEC suggest that this gene could be involved in cell proliferation. Gene HAGE encodes a protein that presents all the motifs of the DEAD box proteins, that are putative ATP-dependent RNA helicases
Affiliations
  • Institution iconUCLouvainMD/MIGE/GECE - Unité de génétique cellulaire

Citations

Martelange, V. (2001). Hage et sage : deux nouveaux gènes exprimés préférentiellement dans les tumeurs. https://hdl.handle.net/2078.5/111100