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 tumor suppressor on chromosome 22, a psv₂neo tagged human chromosome 22 was transferred into the malignant epithelial ovarian cancer cell line, SKOv-3, by micro-cell-mediated chromosome transfer. Complete suppression of the transformed phenotype was observed in 16 of 18 individual microcell hybrid clones as evidenced by the complete abrogation of cell growth under anchorage-independent conditions. In vitro doubling times were also dramatically reduced, as was the ability to form subcutaneous tumors in CD1 nu/nu mice. Only one polymorphic marker, D22S429, segregated with decreased transformation and tumorigenic potential, suggesting that an unrecognized tumor suppressor may localize to chromosome 22q11-q12. These data provide functional support for the presence of a novel tumor suppressor locus (or loci) on chromosome 22 that is important in ovarian cancer tumorigenesis.