IDENTIFICATION OF A MEIOSIS-SPECIFIC PROTEIN AS A MEMBER OF THE CLASSOF CANCER TESTIS ANTIGENS/

Little is known about the function of human cancer/testis antigens (CT As), such as MAGE, BAGE, GAGE, HOM-MEL-40, and NY-ESO-1, the expressio n of which is restricted to human malignancies and testis, When screen ing a cDNA expression library enriched for testis-specific representat ive long transcripts for reactivity with high-titered IgG antibodies f rom the serum of a patient with renal cell carcinoma, one repeatedly d etected antigen, designated HOMTES-14, turned out to be encoded by the synaptonemal complex protein 1 (SCP-1) gene. SCP-1 is known to be sel ectively expressed during the meiotic prophase of spermatocytes and is involved in the pairing of homologous chromosomes, an essential step for the generation of haploid cells in meiosis I. Investigation of a b road spectrum of normal and malignant tissues revealed expression of S CP-1 transcripts and antigen selectively in a variety of neoplastic ti ssues and tumor cell lines. Immunofluorescence microscopy analysis wit h specific antiserum showed a cell cycle phase-independent nuclear exp ression of SCP-1 protein in cancer cells. SCP-1 differs from other mem bers of the class of CTA by its localization on chromosome 1 and its f requent expression in malignant gliomas, breast, renal cell, and ovari an cancer. The aberrant expression of SCP-l in tumors might contribute to their genomic instability and suggests that the functional role of other CTA might also relate to meiosis.