Identification of human testis-specific transcripts and analysis of their expression in tumor cells

Tumor-specific antigens recognized by autologous T lymphocytes are encoded by genes, including those of the MAGE, BAGE, and GAGE gene families, that are expressed in a significant fraction of tumors of various types, but not in normal adult tissues, except for testis where they appear to be expressed in germ cells. Because male germ cells are known to express many genes that are not expressed in other normal adult tissues, we wished to determine whether most of these genes are occasionally activated in tumor cells. Representational difference analysis was used to obtain testis-specific transcripts. The expression of 15 testis-specific cDNA sequences was tested by RT-PCR in a series of tumor cell lines. Only one cDNA sequence showed a significant level of expression in some tumor cell lines. Remarkably, this cDNA clone proved to be a new gene of the MAGE family. These results suggest that MAGE, BAGE, and GAGE genes belong to a minor subset of testis-specific genes that is often activated in tumors of various types, whereas most testis-specific genes are either never or very rarely activated in tumors.