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Identification of Two Candidate Tumor Suppressor Genes on Chromosome 17p13.3¹

Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111 [D. C. S., L. V., D. B. B., T. C. H., A. K. G.], and Department of Microbiology and Immunology, Jefferson Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107 [A. J. W.]

A second tumor suppressor locus on 17p that is distinct from TP53 has 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 OVCA1 and OVCA2, that map to 17p13.3. The two genes are ubiquitously expressed and encode proteins of 443 and 227 amino acids, respectively, with no known functional motifs. Sequence comparison of OVCA1 and OVCA2 revealed extensive sequence identity and similarity to hypothetical proteins from Saccharomyces cerevisiae, Caenorhabditis elegans, and Rattus species. Northern blot analysis reveals that OVCA1 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 conservation, and reduced expression in ovarian tumors and tumor cell lines suggest that decreased expression of these two genes contributes to ovarian tumorigenesis and should be considered candidate tumor suppressor genes.

¹ This work was supported in part by NIH Grant RO1 CA60643 (A. K. G.), the Hoxie Harrison Smith Foundation, the Mary Smith Charitable Lead Trust, Butler Family Fund, Emile Zola Chapter of Brith Shalom Women, and the Ladies Auxiliary to the Veterans of Foreign Wars of the United States of America.

² These authors contributed equally to this work.

³ To whom requests for reprints should be addressed, at Department of Medical Oncology, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111. Phone: (215) 728-2557; Fax: (215) 728-2741.

Received 2/ 8/96. Accepted 3/18/96.

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