Decoding Melanoma Antigen Gene (MAGE) Expression

Melanoma Antigen Genes (MAGEs) are a family of tumor‐associated genes whose protein products share a MAGE‐homology domain (MHD). Type I MAGEs are physiologically restricted in expression to the germline, specifically to the testis, however, they are aberrantly re‐expressed in a wide variety of cancers. Their expression often correlates with poor patient prognosis. There is a significant gap in knowledge regarding the regulatory mechanisms that cause this aberrant expression of Type I MAGEs. The overall goal of this project is to understand these regulatory mechanisms. We have tested the hypothesis that like many germline genes, the expression of the MAGE‐A gene family is regulated by promoter or DNA Methylation. Using DNA Methyltransferase inhibitor 5‐azacytidine, we determined that MAGE‐A gene expression can be controlled by CpG methylation. This data was validated by complementary bioinformatics analysis using the UCSC Genome browser methylome datasets showing conserved differentially methylated positions within the respective promoter regions of target MAGE‐As. In order to test the effect of the aberrant expression, we then introduced MAGE‐A genes into “normal” cells and tested deviations from known phenotypes. We discovered that when expressed several MAGE‐A genes can act as single‐gene drivers of cell proliferation and anchorage‐independent growth. Taken together our data indicate that MAGE‐A genes are expressed by epigenetic mechanisms, specifically CpG methylation and their aberrant expression in cancer is not happenstance but results in providing cells with a proliferative advantage. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in .