Identification of Two Candidate Tumor Suppressor Genes on Chromosome I7pl3.3l

A second tumor suppressor locus on 17p that is distinct from 77*5.1has been identified in brain, breast, lung, and ovarian tumors. Using allelic loss mapping and positional cloning methods, we have recently identified two novel genes, which we refer to as OVCAI and OVCA2, that map to 17pl3.3. The two genes are ubiquitously expressed and encode proteins of 443 and 227 amino acids, respectively, with no known functional motifs. Sequence comparison of OVCAI and OVCA2 revealed extensive sequence identity and similarity to hypothetical proteins from Saccharomyces cer- evisiae, Caenorhabditis elegans, and Rattus species. Northern blot analysis reveals that OVCAI and OVCA2 mRNA were expressed in normal surface epithelial cells of the ovary, but the level of this transcript is significantly reduced or is undetectable in 92% (11/12) of the ovarian tumors and tumor cell lines analyzed. The location, high degree of amino acid con servation, and reduced expression in ovarian tumors and tumor cell lines suggest that decreased expression of these two genes contributes to ovar ian tumorigenesis and should be considered candidate tumor suppressor genes.