LAGE-1, A NEW GENE WITH TUMOR SPECIFICITY

Representational difference analysis was used to identify genes that a re expressed in a human melanoma cell line and not in normal skin. A c DNA clone that appeared to be specific for tumors was obtained and the corresponding gene was sequenced. This new gene was named LAGE-1. Usi ng 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 identi cal to NY-ESO-1, a gene recently reported to code for an antigen recog nized by autologous antibodies in an esophageal squamous cell carcinom a. Gene LAGE-1 maps to Xq28, It comprises 3 exons. Alternative splicin g produces 2 major transcripts encoding polypeptides of 210 and 180 re sidues, respectively. Expression of LAGE-1 was observed in 25-50% of t umor samples of melanomas, non-small-cell lung carcinomas, bladder, pr ostate and head and neck cancers. The only normal tissue that expresse d the gene was testis. As for MACE-AI, 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 stron gly correlated with that of NY-ESO-1. It is also clearly correlated wi th the expression of MAGE genes. (C) 1998 Wiley-Liss, Inc.