Alternative titles; symbols
HGNC Approved Gene Symbol: MAGEA1
Cytogenetic location: Xq28 Genomic coordinates (GRCh38): X:153,179,284-153,183,880 (from NCBI)
Many human melanoma tumors express antigens that are recognized in vitro by cytolytic T lymphocytes (CTLs) derived from the tumor-bearing patient. Van der Bruggen et al. (1991) identified a gene that directs the expression of antigen MZ2-E on a human melanoma cell line, MZ2-MEL, which was derived from patient MZ2. The gene showed no similarity to known sequences. It was expressed by the original melanoma cells, by other melanoma cell lines, and by some tumor cells of other histologic types. No expression was observed in a panel of normal tissues. Antigen MZ2-E appeared to be presented by HLA-A1; anti-MZ2-E CTLs of the original patient recognized 2 melanoma cell lines of other HLA-A1 patients that expressed the gene. Precisely targeted immunotherapy directed against antigen MZ2-E might be provided to individuals identified by HLA typing and analysis of the RNA of a small tumor sample. Chen et al. (1994) identified the MAGE1 gene product by monoclonal and polyclonal antibodies.
Evaluating the expression of each MAGE gene by RT-PCR amplification, De Plaen et al. (1994) found that 6 MAGE genes, including MAGE1, were expressed at a high level in a number of tumors of various histologic types. None was expressed in a large panel of healthy tissues, with the exception of testis and placenta.
Genes of the MAGE family have their entire coding sequences located in the last exon, which shows 64 to 85% identity with that of MAGE1 (De Plaen et al., 1994). (An exception is MAGED2, 300470). The coding sequences predict the main structural features of all MAGE proteins; in contrast, the promoters and first exons of the MAGE genes show considerable variability, possibly enabling the same function to be expressed under different transcriptional controls.
In their annotation of the DNA sequence of the human X chromosome and the predicted proteome, Ross et al. (2005) noted that the MAGE domain was present in 32 genes. In comparison, only 4 other MAGE genes had been reported in the rest of the genome: MAGEF1 (609267) on chromosome 3, and MAGEL2 (605283), NDN (602117), and NDNL2 (608243) in the proximal portion of the long arm of chromosome 15. The MAGE gene products are members of the cancer-testis (CT) antigen group, which are characterized by their expression in a number of cancer types, while their expression in normal tissues is solely or predominantly in testis. This expression profile had led to the suggestion that the CT antigens are potential targets for tumor immunotherapy. Ross et al. (2005) stated that the X chromosome gene set they described contained 99 CT antigen genes, including novel members of the MAGE, GAGE, SSX, LAGE, CSAGE (CSAG1; 300944), and NXF families. Ross et al. (2005) predicted that approximately 10% of the genes on the X chromosome are of the CT antigen type. The remarkable enrichment for CT antigen genes on this chromosome relative to the rest of the genome may be indicative of a male advantage associated with these genes. Recessive alleles that are beneficial to males are expected to become fixed more rapidly on the X chromosome than on an autosome. If these alleles are detrimental to females, their expression could become restricted to male tissues as they rise to fixation. The CT antigen genes on the X chromosome are also notable for the expansion of various gene families by duplication. This degree of duplication is perhaps an indication of selection in males for increased copy number. In this context, it was noted that the MAGE family has independently expanded on the X chromosome in both human and mouse lineages.
Using cDNA and genomic probes in Southern analysis of a human/rodent somatic cell hybrid panel, Wang et al. (1994) mapped MAGE1 and several other members of the multigene family to which it belongs to the long arm of the X chromosome. By fluorescence in situ hybridization, they further localized the gene to Xq28. The other members of the MAGE family located on Xq did not appear to be tandemly linked to MAGE1. By the analysis of hamster/human somatic cell hybrids, however, De Plaen et al. (1994) concluded that the 12 MAGE genes are located in the terminal region of Xq. Southern analysis of somatic cell hybrid DNAs indicated that all the MAGE genes are located on the X chromosome and most are probably in the Xq28 region. Close linkage of most of the MAGE genes was indicated by the fact that several cosmids carried 2 MAGE genes, for example, MAGE3 (300174) and MAGE6 (300176). In the course of a systematic analysis of transcripts in Xq28, Rogner et al. (1995) identified cDNAs related to different MAGE genes. Analysis of cell hybrids, ordered YACs, and cosmids showed that all MAGE genes are located in Xq28 and are clustered in 3 main intervals within 3.5 Mb. The 6 genes expressed in tumors are contained in the 2 intervals closest to the telomere and are highly homologous to each other. Studies in different species suggested that human MAGE sequences are conserved in primates, but less well conserved in other vertebrate species. Rogner et al. (1995) noted that MAGE genes may be implicated in some hereditary disorders that mapped to Xq28, such as dyskeratosis congenita (DKC; 305000).
Chen, Y.-T., Stockert, E., Chen, Y., Garin-Chesa, P., Rettig, W. J., van der Bruggen, P., Boon, T., Old, L. J. Identification of the MAGE-1 gene product by monoclonal and polyclonal antibodies. Proc. Nat. Acad. Sci. 91: 1004-1008, 1994. [PubMed: 8302824] [Full Text: https://doi.org/10.1073/pnas.91.3.1004]
De Plaen, E., Arden, K., Traversari, C., Gaforio, J. J., Szikora, J.-P., De Smet, C., Brasseur, F., van der Bruggen, P., Lethe, B., Lurquin, C., Brasseur, R., Chomez, P., De Backer, O., Cavenee, W., Boon, T. Structure, chromosomal localization, and expression of 12 genes of the MAGE family. Immunogenetics 40: 360-369, 1994. [PubMed: 7927540] [Full Text: https://doi.org/10.1007/BF01246677]
Rogner, U. C., Wilke, K., Steck, E., Korn, B., Poustka, A. The melanoma antigen gene (MAGE) family is clustered in the chromosomal band Xq28. Genomics 29: 725-731, 1995. [PubMed: 8575766] [Full Text: https://doi.org/10.1006/geno.1995.9945]
Ross, M. T., Grafham, D. V., Coffey, A. J., Scherer, S., McLay, K., Muzny, D., Platzer, M., Howell, G. R., Burrows, C., Bird, C. P., Frankish, A., Lovell, F. L., and 270 others. The DNA sequence of the human X chromosome. Nature 434: 325-337, 2005. [PubMed: 15772651] [Full Text: https://doi.org/10.1038/nature03440]
van der Bruggen, P., Traversari, C., Chomez, P., Lurquin, C., De Plaen, E., Van den Eynde, B., Knuth, A., Boon, T. A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science 254: 1643-1647, 1991. [PubMed: 1840703] [Full Text: https://doi.org/10.1126/science.1840703]
Wang, M. G., Zakut, R., Yi, H., Rosenberg, S., McBride, O. W. Localization of the MAGE1 gene encoding a human melanoma antigen to chromosome Xq28. Cytogenet. Cell Genet. 67: 116-119, 1994. [PubMed: 8039421] [Full Text: https://doi.org/10.1159/000133810]