BRCA1 and BRCA2 mutations account for a large proportion of ovarian carcinoma cases.

Authors

Tuya Pal MD
Jenny Permuth-Wey MS
Judith A. Betts RN
Jeffrey P. Krischer PhD
James V. Fiorica MD
Hector Arango MD
James LaPolla MD
Mitchel S. Hoffman MD
Martin A. Martino MD, Lehigh Valley Health NetworkFollow
Katie Wakeley MD
George D. Wilbanks MD
Santo Nicosia MD
Alan B. Cantor PhD
Rebecca Sutphen MD

Publication/Presentation Date

12-15-2005

Abstract

BACKGROUND: It is believed that BRCA1 and BRCA2 germline mutations account for the majority of hereditary ovarian carcinomas; however, to the authors' knowledge, there are scant data on the prevalence and spectrum of mutations, genotype/phenotype correlations, tumor histology, and family history characteristics. To address this gap, the authors conducted a population-based study of 232 incident epithelial ovarian carcinomas in the Tampa Bay area.

METHODS: Genetic testing for the BRCA1 and BRCA2 genes was performed through full sequencing and BRCA1 rearrangement testing.

RESULTS: Of 209 women with invasive ovarian carcinoma, 32 women (15.3%) had mutations in BRCA1 or BRCA2, including 20 BRCA1 mutations and 12 BRCA2 mutations. Of the BRCA2 mutations, 58% were outside the "ovarian cancer cluster region" (OCCR). Variants of uncertain significance were detected in 8.2% of women with invasive ovarian carcinoma. No mutations were identified in women with borderline or invasive mucinous tumors. Among the BRCA mutation-positive women, 63% had serous tumors. A family history of breast and/or ovarian carcinoma was reported in 65%, 75%, and 43.5% of relatives of BRCA1 carriers, BRCA2 carriers, and non-BRCA1/BRCA2 carriers, respectively.

CONCLUSIONS: The data from this study suggested that 1) previous studies may have underestimated the frequency of BRCA1 and BRCA2 mutations in ovarian carcinomas, especially outside the OCCR; 2) it may be reasonable to offer genetic counseling to any woman with an invasive, nonmucinous epithelial ovarian tumor; and 3) among patients with invasive ovarian carcinoma, family history is not sufficiently accurate to predict mutation status.

Volume

104

Issue

12

First Page

2807

Last Page

2816

ISSN

0008-543X

Published In/Presented At

Pal T., Permuth-Wey J., Betts JA., Krischer JP., Fiorica J, Arango H., LaPolla J., Hoffman M., Martino MA., Wakeley K., Wilbanks G., Nicosia S., Cantor A., Sutphen R. (2005). BRCA1 and BRCA2 mutations account for a large proportion of ovarian carcinoma cases. Cancer, 104(12), 2807-2816.

Disciplines

Obstetrics and Gynecology

PubMedID

16284991

Department(s)

Department of Obstetrics and Gynecology, Department of Obstetrics and Gynecology Faculty

Document Type

Article