The MMAI gene family of cancer-testis antigens has multiple alternative splice variants:: Characterization of their expression profile, the genomic organization, and transcript properties

Previously, we reported the identification of MMA IA by screening for differential gene expression in two human melanoma cell lines displaying diverse metastatic behavior after subcutaneous inoculation into nude mice. Splice variant MMA IB, which also was identified through database homology searches, showed a high degree of similarity with the MMA IA for exons 1, 2, and 4, but was missing exon 3. Through extensive expression profiling among normal and tumor samples, both MMA IA and - IB were found to belong to the family of cancer-testis antigens. In this study, we identified four additional alternatively spliced MMA IA variants, named MMA IC, MMA ID, MMA IE, and MMA IF. Generally, these novel MMA I transcripts differ from MMA IA in that exon 2 or exon 3 is enlarged because of the use of alternative splice sites in intron 2 of the MMA I gene. Moreover, MMA IE also lacks exon 3, as was previously seen in MMA IB. In screening for expression of the novel MMA I transcripts in normal and tumor tissues, we demonstrated that MMA IC, - ID, and - IE also are members of the cancer-testis antigen family. MMA IF was found in only one melanoma metastasis sample and therefore is believed to have been expressed incidentally. Furthermore, we comprehensively elucidated the genomic structure of the MMA I gene and the characteristic features of the alternatively spliced MMA I transcripts. (C) 2004 Wiley-Liss, Inc.