LAGE-1, a new gene with tumor specificity

Abstract

Representational difference analysis was used to identify genes that are expressed in a human melanoma cell line and not in normal skin. A cDNA clone that appeared to be specific for tumors was obtained and the corresponding gene was sequenced. This new gene was named LAGE‐1. Using a LAGE‐1 probe to screen a cDNA library from the same melanoma cell line, we identified a closely related gene, which proved to be identical to NY‐ESO‐1, a gene recently reported to code for an antigen recognized by autologous antibodies in an esophageal squamous cell carcinoma. Gene LAGE‐1 maps to Xq28. It comprises 3 exons. Alternative splicing produces 2 major transcripts encoding polypeptides of 210 and 180 residues, respectively. Expression of LAGE‐1 was observed in 25–50% of tumor samples of melanomas, non‐small‐cell lung carcinomas, bladder, prostate and head and neck cancers. The only normal tissue that expressed the gene was testis. As for MAGE‐A1, expression of LAGE‐1 is induced by deoxy‐azacytidine in lymphoblastoid cells, suggesting that tumoral expression is due to demethylation. The expression of LAGE‐1 is strongly correlated with that of NY‐ESO‐1. It is also clearly correlated with the expression of MAGE genes. Int. J. Cancer 76:903–908, 1998.