Functional evidence for an ovarian cancer tumor suppressor gene on chromosome 22 by microcell-mediated chromosome transfer

The identity of many tumor suppressor genes important in epithelial ovarian cancer tumorigenesis remains unknown. In an effort to localize a novel tum or suppressor on chromosome 22, a psv(2)neo tagged human chromosome 22 was transferred into the malignant epithelial ovarian cancer cell line, SKOV-3, by microcell-mediated chromosome transfer. Complete suppression of the tra nsformed phenotype was observed in 16 of 18 individual microcell hybrid clo nes as evidenced by the complete abrogation of cell growth under anchorage- independent conditions. In vitro doubling times were also dramatically redu ced, as was the ability to, form subcutaneous tumors in CD1 nu/nu mice. Onl y one polymorphic marker, D22S429, segregated with decreased transformation and tumorigenic potential, suggesting that an unrecognized tumor suppresso r may localize to chromosome 22q11-q12, These data provide functional suppo rt for the presence of a novel tumor suppressor locus (or loci) on chromoso me 22 that is important in ovarian cancer tumorigenesis.