CLONING A NOVEL MEMBER OF THE HUMAN INTERFERON-INDUCIBLE GENE FAMILY ASSOCIATED WITH CONTROL OF TUMORIGENICITY IN A MODEL OF HUMAN-MELANOMA

Chromosome 6-mediated suppression of tumorigenicity in malignant melan oma cell lines provides a model system to identify genes associated wi th the reversion of the tumorigenic phenotype. Using subtractive cDNA selection, we recently identified a series of novel genes which are di fferentially expressed in association with chromosome 6-mediated suppr ession. We now report the molecular characterization of a novel gene t ermed AIM2 for (Absent In Melanoma), which represents a 1485 bp cDNA. An open reading frame of 1032 base pairs, corresponding to 344 amino a cid residues, is predicted. The predicted protein shares a conserved s equence domain of approximately 200 amino acids with known interferon- inducible genes of both human and mouse. We demonstrate that the AIM2 gene encodes a transcript of approximately 2 kb which is expressed in spleen, small intestine, and peripheral blood leukocytes. In addition, we have localized AIM2 to the long arm of human chromosome 1 (band q2 2) in a highly conserved region which also contains the known interfer on-inducible genes IFI16 and MNDA. We have also demonstrated that, lik e IFI16 and MNDA, AIM2 is induced in HL60 cells by interferon gamma. O ur findings support the existence of a family of genes in this region similar to the well-characterized mouse Ifi200 gene family.