IDENTIFICATION OF 2 CANDIDATE TUMOR-SUPPRESSOR GENES ON CHROMOSOME 17P13.3

A second tumor suppressor locus on 17p that is distinct from TP53 has been identified in brain, breast, lung, and ovarian tumors. Using alle lic loss mapping and positional cloning methods, we have recently iden tified two novel genes, which we refer to as OVCA1 and OVCA2, that map to 17p13.3. The two genes are ubiquitously expressed and encode prote ins of 443 and 227 amino acids, respectively, with no known functional motifs. Sequence comparison of OVCA1 and OVCA2 revealed extensive seq uence identity and similarity to hypothetical proteins from Saccharomy ces cerevisiae, Caenorhabditis elegans, and Rattus species, Northern b lot analysis reveals that OVCA1 and OVCA2 mRNA were expressed in norma l surface epithelial cells of the ovary, but the level of this transcr ipt is significantly reduced or is undetectable in 92% (11/12) of the ovarian tumors and tumor cell lines analyzed. The location, high degre e of amino acid conservation, and reduced expression in ovarian tumors and tumor cell lines suggest that decreased expression of these two g enes contributes to ovarian tumorigenesis and should be considered can didate tumor suppressor genes.