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BRCA1 Gene Mutations in Sporadic Ovarian Carcinomas: Detection by PCR and Reverse Allele-specific Oligonucleotide Hybridization

¹ Department of Obstetrics and Gynecology, Division of Gynecology, and
² Department of Clinical Pathology, General Hospital of Vienna, University of Vienna, A-1090 Vienna, Austria.

³ Ludwig-Boltzmann Institute for Oncology and Fertility Treatment, A-1090 Vienna, Austria.
^a Address correspondence to this author at: General Hospital of Vienna, Department of Obstetrics and Gynecology, Molecular Oncology Group, Währinger Gürtel 18-20, EBO 05, A-1090 Vienna, Austria. Fax 43-1-40400-7832; e-mail robert.zeillinger{at}akh-wien.ac.at

Background: Although germline mutations in BRCA1 play a central role in familial breast and ovarian cancers, to date, no somatic mutations in BRCA1 have been reported in sporadic breast cancer, and only five somatic mutations have been identified in the sporadic ovarian carcinomas. Because loss of heterozygosity appears frequently at the BRCA1 locus in nonfamilial breast and ovarian carcinomas, we searched for mutations in the BRCA1 gene in sporadic ovarian tumors.

Methods: We developed a detection system based on PCR and reverse allele-specific oligonucleotide hybridization on membrane strips for the simultaneous detection of 17 frequently occurring mutations in the BRCA1 gene.

Results: As little as 2% mutant DNA in a sample could be detected. Two of 122 DNA samples isolated from sporadic ovarian tumor biopsies contained the Cys61Gly mutation. Both mutations were germline mutations. One of these was an ovarian metastasis of a primary fallopian tube carcinoma. The tubal carcinoma was also confirmed to contain the Cys61Gly mutation.

Conclusions: This is the first report that a germline BRCA1 mutation is associated with primary tubal carcinoma. The 17 specific mutations in the BRCA1 gene do not play a major role in the tumorigenesis and progression of sporadic ovarian cancer.© 1999 American Association for Clinical Chemistry

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