Abstract

Multiple chromosome 17 loci may be involved in ovarian carcinogenesis. Fifty-seven sporadic ovarian epithelial tumors were examined for loss of heterozygosity at 15 loci on chromosome 17p. Eighty % (39 of 49) of informative tumors had allelic loss in 17p13.3 at D17S30, D17S28 , or both loci within this region, including 3 of 7 tumors of low malignant potential and 4 of 5 nonmetastatic carcinomas. The smallest region of overlapping deletion extends from D17S28 to D17S30 , a distance of 15 kb. Furthermore, several tumors have breakpoints within the region detected by the D17S30 probe. Chromosome 17p13.3 genes with potential tumor suppressor function include HIC-1 , DPH2L (N. J. Philips et al. Isolation of a human diphthamide biosynthesis gene on chromosome 17p13.3, submitted for publication)/ OVCA1 , PEDF , and CRK . The HIC-1 coding sequence lies 1 kb centromeric to the D17S28-S17S30 region of deletion (M. Makos Wales et al. , Nat. Med., 1 : 570–577, 1995) but remains a candidate because 5'-regulatory elements may lie within the critical region. Portions of the DPH2L/OVCA1 coding sequence lie within the D17S28-D17S30 interval. Somatic cell hybrid analysis places PEDF in an interval including D17S28 , D17S30 , and D17S654 , whereas CRK is excluded from this interval. Chromosome 17p13.3 loss precedes TP53 and BRCA1 region deletions because the latter changes are seen only in high-stage carcinomas. Microsatellite instability plays only a minor role in sporadic ovarian carcinogenesis because only 1 of 57 tumors showed this finding. 1 Supported in part by Gynecological Oncology Group/NIH grants Ca-274-69-10 (to N. J. P.), VA RAG (to D. M. R.), and NIH HG00469 (to H. D-K.). 2 To whom requests for reprints should be addressed, at Department of Pathology, Saint Louis University Hospital, 3635 Vista Avenue, St. Louis, MO 63110.