Disease relevance of MAGED4

• MAGED4 was expressed in 30% of RCC and both glioblastoma samples [1].
• MAGED4-expression in renal cell carcinoma and identification of an HLA-A*25-restricted MHC class I ligand from solid tumor tissue [1].
• Contrasting frequencies of antitumor and anti-vaccine T cells in metastases of a melanoma patient vaccinated with a MAGE tumor antigen [2].
• MAGE-E1, a new member of the melanoma-associated antigen gene family and its expression in human glioma [3].
• CT10: a new cancer-testis (CT) antigen homologous to CT7 and the MAGE family, identified by representational-difference analysis [4].

High impact information on MAGED4

• A subset of highly homologous MAGE genes (group A; MAGE-A) belong to the chromosome X-clustered cancer/testis antigens [5].
• We report here that these CpG are demethylated in the tumor cell lines that express MAGE-1, and are methylated in those that do not express the gene [6].
• The two major MAGE-1 promoter elements have an Ets binding site, which contains a CpG dinucleotide [6].
• Besides antigens known to elicit T-cell responses, such as MAGE-1 and tyrosinase, numerous additional antigens that were overexpressed or specifically expressed in tumors of the same type were identified [7].
• MAGE-Xp is expressed only in testis and, unlike the Xq27-qter MAGE genes, it is not expressed in any of 12 different tumor tissues tested [8].

Chemical compound and disease context of MAGED4

• METHODS: We evaluated promoter demethylation status of the MAGE-A1 and MAGE-A3 genes by RT-PCR analysis and methylation-specific PCR (MS-PCR), as well as sequencing analysis, after sodium bisulfite modification in 32 colorectal cancer cell lines and 87 cancer tissues [9].
• The tumour-associated antigen MAGE-1 is detectable in formalin-fixed paraffin sections of malignant melanoma [10].

Biological context of MAGED4

• Three alternatively spliced variants (MAGE-E1a-c) were found, and deduced amino acid sequence showed that MAGE-E1a and -E1b shared the MAGE-conserved region, whereas -E1c did not [3].
• Tissue distribution analysis showed that MAGE-E1 was distinct from other MAGEs [3].
• Expressed sequence tags containing this tag were homologous to the melanoma-associated antigen gene (MAGE) family, and this new cDNA, named MAGE-E1, was cloned by the 5'-rapid amplification of cDNA ends technique [3].
• The open reading frame encoding the MAGE-E1 peptides initiates in exon 2 and ends in exon 13 [11].
• The MAGE-E1 gene is composed of 13 exons, and three of these (exon 2, exon 3 and exon 12) are alternatively spliced in each variant (E1a-c) [11].

Anatomical context of MAGED4

• Real-time quantitative reverse transcription-PCR showed that MAGE-E1 expression was 2.6-15-fold enriched in glioblastoma relative to human astrocytes [3].
• The four new MAGE genes are not expressed in normal tissues, except for testis, and are expressed in tumors of different histological origins [12].
• The tumor origin of the cell lines was supported by the expression of the ErbB2 oncogene (seven of nine) and MAGE mRNA (eight of eight) [13].
• The first human members of the MAGE gene family that have been described are expressed in tumor cells but silent in normal adult tissues except in the male germ line [14].
• Analysis of primary prostate cancer revealed MAGE expression patterns considerably concordant with those found in the corresponding bone marrow aspirates [15].

Associations of MAGED4 with chemical compounds

• Treatment with the DNA hypomethylating agent 5-aza-2'-deoxycytidine induced and up-regulated the mRNA expression of MAGE-1 and epitope presentation by autologous MHC [16].
• The expression of cell cycle regulatory transcription factors E2F4 and the MAGE protein necdin were similarly altered in all subjects after rosiglitazone treatment [17].
• The metabolic control of 11 brittle diabetic subjects, as assessed by the M value and the MAGE index (used as indexes of blood glucose control and of glycemic fluctuations, respectively), was compared during a 5-day period before and after a 24-h connection to the artificial pancreas [18].
• In further analysis, we showed that treatment with brefeldin A or paraformaldehyde fixation of Epstein-Barr virus-transformed B cells prevented the presentation of the Mage 1 T cell epitope, which excluded extracellular processing of the antigen [19].
• Subsequent to sodium bisulfite modification and MS-PCR analysis, the promoter hypomethylation of MAGE-A1 and MAGE-A3 was confirmed in both at 81% each [9].

Other interactions of MAGED4

• These results suggest that MAGE-D and -E1 may be evolutionarily distant from other members of the MAGE family, and the two may be ancestral genes for the others [11].

Analytical, diagnostic and therapeutic context of MAGED4

• We have also demonstrated that the MAGE-E1 gene is located in Xp11 through the analysis of radiation hybrid panels [11].
• We have previously identified novel members of the MAGE gene family expressed in human glioma and named them MAGE-E1a-c. In the present study, we have revealed the genomic structure of MAGE-E1 by sequence analysis of a human chromosome bacterial artificial chromosome clone containing the MAGE-E1 gene [11].
• These results indicate that Hodgkin disease may be a target for specific immunotherapy involving MAGE-A4 antigens [20].
• Moreover, MAGE-positive bone marrow samples from a small group of seven sarcoma patients demonstrated the relevance of our multimarker RT-PCR in nonepithelial tumors [15].
• Despite extensive studies, however, CD8+ T-cell responses to MAGE-derived epitopes have been detected only occasionally in cancer patients, even after vaccination [21].

References