MAPPING OF CHROMOSOME 3P DELETIONS IN HUMAN EPITHELIAL OVARIAN-TUMORS

Epithelial ovarian tumors frequently display deletions on the short ar m of chromosome 3 suggesting the existence of tumor suppressor genes w ithin the deleted regions. We have recently established a primary tiss ue culture system as a model to investigate the genetic events associa ted with ovarian cancer. The frequencies of loss of heterozygosity (LO H) at 16 loci representative of chromosome 3p in 33 tumor biopsies and 47 ovarian primary cultures derived from unselected ovarian cancers w ere examined, This repertoire also included benign and borderline tumo rs as well as malignant ovarian ascites, LOH was observed in 25 (31%) samples for at least one marker: 21 of 58 malignant, two of 12 borderl ine and two of 10 benign specimens, Chromosome 3p loss was not restric ted to ovarian tumors of high grade and stage. LOH was observed in bot h cultured and non cultured tumors and ascites, A spontaneously immort alized cell line derived from a malignant ovarian ascites, OV-90, disp layed LOH of the majority of markers suggesting loss of one homolog of chromosome 3p, The pattern of deletion displayed by these 25 samples enabled the determination of at least two distinct regions of overlapp ing deletions on chromosome 3p extending from D3S1270 to D3S1597 and f rom D3S1293 to D3S1283, In addition, a region proximal to D3S1300 was deleted in a subset of samples. Although loss of loci overlapping thes e three regions (Regions I, II and III) were observed in malignant and benign tumors, in borderline tumors loss was observed of markers repr esentative of Region III only. While RAR beta is presently included in Region II, the minimal regions of deletion exclude VHL, TGFBR2, PTPas ey and FHIT as candidate tumor suppressors in ovarian tumorigenesis.