Expression profiling of MMA-1a and splice variant MMA-1b: new cancer/testis antigens identified in human melanoma.
Using high-density oligonucleotide array analysis, we have recently compared the gene expression profiles of 2 human melanoma cell lines with marked difference in metastatic behavior after subcutaneous inoculation into nude mice (de Wit et al., Melanoma Res, in press). We identified an expressed sequence tag (EST), which we called malignant melanoma-associated 1 (MMA-1a), showing evident differential expression between the 2 cell lines. The MMA-1a gene is localized on chromosome 21q22.2 and its mRNA exists of 4 exons. Homology search displayed a splice variant of MMA-1a that lacks exon 3 and that was called MMA-1b. Expression profiles of MMA-1a and MMA-1b are determined by reverse transciptase polymerase chain reaction (RT-PCR) analysis. Among 30 different normal tissue samples, expression of MMA-1a and MMA-1b was exclusively found in the testis after a first PCR of 30 cycles. Even more sensitive screening achieved by performing multiple semi-nested RT-PCR showed no or very low expression in the other normal tissues tested. During melanocytic tumor progression, MMA-1a and/or MMA-1b exhibited an emergence of expression in primary melanoma (20%) and melanoma metastasis samples (30%) after only 1 round of PCR. Expression of MMA-1a and/or MMA-1b was also identified in other tumor cell lines and fresh tumor samples of variable origin, e.g., lung, liver, bladder and soft tissues (sarcomas). We conclude that MMA-1a and MMA-1b are new members of the family of cancer/testis antigens.
de Wit
Nicole J W
NJ
Department of Pathology, University Medical Centre St. Radboud, Nijmegen, The Netherlands. n.dewit@pathol.azn.nl
Weidle
Ulrich H
UH
Ruiter
Dirk J
DJ
van Muijen
Goos N P
GN
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000235:genetics*; D001483:Base Sequence; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid
D000951:Antigens, Neoplasm; D018076:DNA, Complementary; C453740:DSCR8 lncRNA, human; D020033:Protein Isoforms; D012334:RNA, Neoplasm