HOMOZYGOUS DELETIONS ON THE SHORT ARM OF CHROMOSOME-9 IN OVARIAN ADENOCARCINOMA CELL-LINES AND LOSS OF HETEROZYGOSITY IN SPORADIC TUMORS

Rat ovarian surface epithelial cells transformed spontaneously in vitr o have been found to have homozygous deletions of the interferon alpha (IFNA) gene. This suggests that inactivation of a tumor-suppressor ge ne in this region may be crucial for the development of ovarian cancer . We therefore used microsatellite markers and Southern analysis to ex amine the homologous region in humans-the short arm of chromosome 9-fo r deletions in sporadic ovarian adenocarcinomas and ovarian tumor cell lines. Loss of heterozygosity occurred in 34 (37%) of 91 informative sporadic tumors, including some benign, low-malignant-potential and ea rly-stage tumors, suggesting that it is an early event in the developm ent of ovarian adenocarcinoma. Furthermore, homozygous deletions on 9p were found in 2 of 10 independent cell lines. Deletion mapping of the tumors and lines indicates that the candidate suppressor gene inactiv ated as a consequence lies between D9S171 and the IFNA locus, a region that is also deleted in several other tumors and that contains the me lanoma predisposition gene, MLM.