Identification on a human sarcoma of two new genes with tumor-specific expression

Genes MAGE, BAGE, GAGE and LAGE-1/NY-ESO-1 code for antigens that are recog nized on melanoma cells by autologous CTLs, Because the pattern of expressi on of these genes results in the presence of antigens on many tumors of var ious histological types and not on normal tissues, these antigens qualify f or cancer immunotherapy, To identify new genes with tumor-specific expressi on, we applied a cDNA subtraction approach, i.e., representational differen ce analysis, to a human sarcoma cell line. We obtained two cDNA clones that appeared to be tumor specific, The corresponding genes were named SAGE and HAGE because they have the same pattern of expression as genes of the MAGE family. SAGE encodes a putative protein of 904 amino acids and shows no ho mology to any recorded gene. Like the MAGE-A genes, it is located in the q2 8 region of chromosome X. Expression of gene SAGE was observed mainly in bl adder carcinoma, lung carcinoma, and head and neck carcinoma but not in nor mal tissues, with the exception of testis, Gene MAGE, which is located on c hromosome 6, encodes a putative protein of 648 amino acids. This protein is a new member of the DEAD-box family of ATP-dependent RNA helicases. Gene H AGE is expressed in many tumors of various histological types at a level th at is 100-fold higher than the level observed in normal tissues except test is, Because of this tumor-specific expression, genes SAGE and HAGE ought to encode antigens that could be useful for antitumoral therapeutic vaccinati on.