VERY FREQUENT LOSS OF HETEROZYGOSITY THROUGHOUT CHROMOSOME-17 IN SPORADIC OVARIAN-CARCINOMA

Frequent loss of heterozygosity (LOH) on both arms of chromosome 17 has been described in ovarian carcinoma (OC) by a number of groups, and the recent fine mapping of an inherited breast-ovarian cancer gene (brcA1) to a small region at 17q12-21 has focused interest on this area. We studied 28 sporadic OCs with 21 markers at 18 loci on chromosome 17 (S on 17p and 13 on 17q). LOH on 17p was 78%, and always involved pS3. In 86% of cases showing LOH, all informative markers on chromosome 17 showed reduction to homozygosity. Using 6 markers flanking the brcAl locus on 17q, LOH was 75%, but only one tumour showed LOH with telomeric retention. The data therefore suggest that small deletions on chromosome 17 are very uncommon in sporadic OC. No genomic rearrangements by Southern blotting were seen in the brcAl candidate gene estradiol 17beta dehydrogenase 2 (17hsd2), or in erbB2, prohibitin (phb) and nmel (previously nm23-H1). LOH on chromosome 17 was more common in high-grade, late-stage carcinomas, and no LOH was seen in any benign or borderline tumour. This study has clearly demonstrated that LOH at any one site on chromosome 17 is most commonly explained by LOH over the whole of the chromosome. We consider possible reasons for the absence of small deletions on chromosome 17 in OC.