Evaluation of melanoma antigen (MAGE) gene expression in human cancers using The Cancer Genome Atlas

Melanoma antigen (MAGE) cancer-testis (CT) (or cancer-germline) genes are frequently over-expressed in cancer. However, the types of cancer in which the MAGE genes are over-expressed and the effect of over-expression on outcomes have been difficult to ascertain, and their relevance to progression is unclear. We queried transcriptomic and survival data from 26 cancer studies through the cBio Cancer Genomics Portal (www.cbioportal.org) to investigate dysregulation of 34 MAGE genes in cancer. MAGE genes are dysregulated in many cancers. Up to 44% of samples had over-expression of 22 Type 1 MAGE, which are not expressed in most normal tissues, or dysregulation of 12 Type 2 MAGE genes, which are expressed in normal tissues. Dysregulation of specific MAGE genes correlated with reduced overall survival in four cancer types (brain low grade gliomas, renal clear cell carcinomas, head and neck squamous cell carcinomas, and uterine corpus endometrioid carcinomas), with weaker correlations in four additional cancer types. This study demonstrates (1) the value of cancer-germline antigen expression profiling as a complement to mutation analysis for prognosis in cancer; (2) that over-expression of MAGE genes in a subset of cancers is associated with reduced survival; and (3) that patterns of MAGE expression could inform individualized treatment in cancer.