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Division of Gynecologic Oncology, Department of Obstetrics and Gynecology [H. T., K. B., P. E. M., H-C. C., A. W. M., P. C. L., I. B., M. A. M., S. A. K., B. A. R., A. C., J. J. M., S. C. R., J. B.], Division of Hematology-Oncology, Department of Medicine [F. J. C., B. L. W.], Surgical Pathology Section, Department of Pathology and Laboratory Medicine [V. A. L.], and University of Pennsylvania Medical Center and University of Pennsylvania Comprehensive Cancer Center [B. L. W., V. A. L., I. B., M. A. M., J. J. M., S. C. R., J. B.], Philadelphia, Pennsylvania 19104; Department of Molecular and Cell Biology and School of Public Health, University of California, Berkeley, California 94720 [L. S. F., M-C. K.]; and Department of Pathology, Jikei University School of Medicine, Tokyo 105, Japan [M. F.]
Germline mutations of the BRCA1 tumor suppressor gene on chromosome 17q are involved in a significant fraction of hereditary breast and ovarian cancers. Allelic deletions that include the BRCA1 locus are common in breast and ovarian cancers, implying that somatic mutations of this gene may play an important role in the more common sporadic forms of these tumors as well. The recent cloning of BRCA1 allows direct testing of this hypothesis. A combination of single strand conformation and sequencing analyses was used to examine the 22 coding exons and intronic splice donor and acceptor regions of BRCA1 for mutations in 115 unselected cases of epithelial ovarian carcinoma. Seven mutations were identified, all of which were present in the germlines of patients with remarkable family or medical histories of breast and/or ovarian cancer. Eighty-nine of these tumors were examined for loss of heterozygosity in the BRCA1 region of chromosome 17q, and 67% of the tumors studied exhibited allelic deletions that included this region. These data are consistent with the hypothesis that BRCA1 mutations are involved in the etiology of hereditary ovarian carcinomas but occur rarely in sporadic tumors, and that the frequent allelic loss on chromosome 17q in this cancer type reflects the involvement of an additional tumor suppressor gene(s).
1 To whom requests for reprints should be addressed, at Department of Obstetrics and Gynecology, University of Pennsylvania Medical Center, 778 Clinical Research Building, 415 Curie Boulevard, Philadelphia, PA 19104.
Received 4/ 6/95. Accepted 6/ 1/95.
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