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[Cancer Research 60, 5329-5333, October 1, 2000]
© 2000 American Association for Cancer Research

Advances in Brief

BRCA1 Promoter Region Hypermethylation in Ovarian Carcinoma: A Population-based Study1

Rae Lynn Baldwin2, Elizabeta Nemeth, Hang Tran, Hyun Shvartsman, Ilana Cass, Steven Narod and Beth Y. Karlan

Division of Gynecologic Oncology, The Burns and Allen Research Institute, Cedars-Sinai Medical Center, Los Angeles, California 90048 [R. L. B., E. N., H. T., H. S., I. C., B. Y. K.]; Department of Obstetrics and Gynecology, University of California, Los Angeles, California 90095-1740 [R. L. B., I. C., B. Y. K.]; and The Centre for Research in Women’s Health, Toronto, Ontario, M5G 1N8 Canada [S. N.]

There is a clear association between germ-line BRCA1 mutations and inherited ovarian cancer; however, the association between BRCA1 mutations and sporadic ovarian cancer remains ambiguous. The frequency of BRCA1 promoter hypermethylation as an epigenetic means of BRCA1inactivation was determined for a large, population-based cohort of ovarian cancer patients. BRCA1 promoter hypermethylation was determined by methylation-specific restriction digestion of tumor DNA, followed by Southern blot analysis and confirmed by methylation-specific PCR. BRCA1 promoter hypermethylation was observed in 12 of 98 ovarian tumors. BRCA1 methylation status of the primary tumor was conserved in six recurrent tumors after interim chemotherapy. None of the 12 tumors with BRCA1 promoter hypermethylation demonstrated BRCA1 protein expression by immunohistochemistry. BRCA1 methylation was only seen in ovarian cancer patients without a family history suggestive of a breast/ovarian cancer syndrome. Therefore, the 12 BRCA1methylated tumors represented 15% (12 of 81) of the sporadic cancers analyzed in this study. Although the clinical significance of BRCA1 promoter hypermethylation is yet to be determined, promoter hypermethylation may be an alternative to mutation in causing the inactivation of the BRCA1 tumor suppressor gene in sporadic ovarian cancer.




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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
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Copyright © 2000 by the American Association for Cancer Research.