Identification of Two Candidate Tumor Suppressor Genes on Chromosome 17p13.3: Assessment of Their Roles in Breast and Ovarian Carcinogenesis
Abstract
Loss of all or part of one copy of chromosome l7p is a frequent event in breast and ovarian tumors. We identified a common region of allelic loss between two highly polymorphic DNA markers on l7pl3.3, YNH37.3 and YNZ22.l. These two markers are separated by less than 20 kbp. To date, only two genes have been reported that map within the critical region, OVCAl and OVCA2. Both OVCAl and OVCA2 are highly conserved evolutionarily. Western blotting and immunohistochemical approaches reveal that OVCAl - and OVCA2 is expressed in normal mammary and ovarian epithelium, and that their levels are significantly reduced or are undetectable in a high percentage of tumors and tumor cell lines. Somatic mutations are rare in OVCAl and OVCA2, however, two germline missense mutations have been found in breast cancer- prone women who have tested negative for a BRCAl or a BRCA2 mutation. Over-expression of OVCAl, but not OVCA2 appears to suppress breast and ovarian tumor cell growth in vitro. Screens for proteins that potentially interact with OVCAl have uncovered a novel RNA binding protein, called BOV-l. Our goals are to evaluate the biochemical functions of OVCAl and OVCA2 and determine their potential role(s) in breast and ovarian oncogenesis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1999
- Accession Number
- ADB249637
Entities
People
- Andrew K. Godwin
Organizations
- Fox Chase Cancer Center