Activation of melanoma antigen tumor antigens occurs early in lung carcinogenesis

The melanoma antigen (MAGE)-encoding genes are expressed in various tumor t ypes, including lung, and are thought to be silent in all normal tissues ex cept testis. In search of biomarkers for early lung cancer detection and ca ncer risk assessment we investigated frequencies of expressional activation of MAGE-A1, -A3, and -B2 genes in non-small cell lung cancers (NSCLCs). Ex pression of these genes was evaluated by reverse transcription-PCR (RT-PCR) in 20 primary NSCLC samples and corresponding normal lung tissues as well as in 20 bronchial brush specimens from former smokers without lung cancer. mRNA in situ hybridization was done to confirm the gene expression pattern at the cellular level. Methylation-specific PCR was performed to evaluate the hypomethylation status of CpG sites in the promoter regions of these ge nes. Among the 20 primary NSCLC samples analyzed, 14 (70%) expressed MAGE-A 1 and 17 (85%) each expressed MAGE-A3 and MAGE-B2. A substantial number of normal lung tissues adjacent to NSCLC also had a detectable level of MAGE e xpression (65, 75, and 80% for MAGE-A1, -A3, and -B2, respectively). We fou nd that 7 (35%), 10 (50%), and 11 (55%) of the adjacent normal lung tissue samples exhibited promoter hypomethylation at MAGE-A1, -A3, and -B2, respec tively, compared with 15 (75%), 16 (80%), and 16 (80%) of the NSCLC samples . Among the 20 bronchial epithelium samples from former smokers, 7 (35%), 1 0 (50%), and 12 (60%) had also detectable -A1, -A3, and -B2 expression, res pectively. Activation of MAGE-A1, -A3, and -B2 genes is common not only in NSCLC but also in bronchial epithelium with severe carcinogen insult. These results suggest that MAGE genes may be activated very early in lung carcin ogenesis and may be considered as targets for lung cancer prevention.