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A Deletion Unit on Chromosome 17q in Epithelial Ovarian Tumors Distal to the Familial Breast/Ovarian Cancer Locus

Cancer Research Campaign Human Cancer Genetics Group, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, United Kingdom [I. J. J., S. A. S., T. H., B. A J. P.]; Department of Obstetrics and Gynaecology, University of Cambridge, Rosie Maternity Hospital, Robinson Way, Cambridge CB2 2SW, United Kingdom [I. J. J.]; Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina 27709 [R. W. W., P. A. F.]; Departments of Clinical Oncology [R. J. O.] and Pathology [A. M.], University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 2QQ, United Kingdom; and Departments of Gynecologic Oncology [A. B.] and Medicine [R. C. B.], Microbiology and Immunology, Duke University Medical Center and Duke Comprehensive Cancer Center, Durham, North Carolina 27710

Linkage analysis in familial breast and ovarian cancer and studies of allelic deletion in sporadic ovarian tumors have suggested that chromosome 17q may be the location of a gene of importance in ovarian carcinogenesis. We have examined tumor and normal DNA samples from 120 patients with ovarian tumors for allelic deletion at 12 loci on chromosome 17q. Allelic deletion was observed in 64 cases (53%) of which 56 showed loss of heterozygosity at all loci analyzed on 17q. The pattern of allele loss at metastatic sites was consistent with loss of heterozygosity having occurred prior to metastasis. A common region of deletion, defined by 6 cases of invasive epithelial ovarian cancer and a benign serous cystadenoma, spanned 16 cM and was delimited by nm23 and GH. This region is distal to the region on chromosome 17q to which the familial breast/ovarian cancer susceptibility gene has been mapped. The results suggest that a tumor suppressor gene involved in sporadic ovarian carcinogenesis is located on the distal portion of chromosome 17q and is distinct from the gene linked to familial cases.

¹ Cancer Research Campaign McElwain Fellow in Gynaecologic Oncology and supported in part by a Medical Research Council Travelling Fellowship.

² Supported by the Cancer Research Campaign.

³ Cancer Research Campaign Professor of Human Cancer Genetics.

Received 11/30/92. Accepted 2/ 2/93.

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