Åke Borg
Principal investigator
BRCA1 and BRCA2 mutations in ovarian cancer : Covariation with specific cytogenetic features
Author
Summary, in English
We analyzed 37 primary invasive carcinomas for BRCA1 and BRCA2 mutations by screening the entire coding regions of both genes. Seven predicted truncating mutations (four in BRCA1 and three in BRCA2) and one novel BRCA1 missense variant (S1542C) were identified (8/37, 22%). Two of the BRCA1 mutations were somatic changes, whereas the remaining three BRCA1 changes and all mutations of BRCA2 were found to be of germline origin. All eight BRCA-positive tumors were serous or seropapillary carcinomas (8/27 serous tumors, 30%), and all but one were poorly differentiated. The correlation between tumor karyotype and BRCA status showed that clonal chromosomal aberrations were present in all BRCA-positive tumors (8/8) compared with 20 of 29 BRCA-negative ones. The most consistently affected region in BRCA-positive tumors was the long arm of chromosome 6; alterations within this arm with a breakpoint in band 6q21 were seen in four of five BRCA1-positive and in two of three BRCA2-positive tumors, but only in four of 20 karyotypically abnormal tumors without BRCA mutations, suggesting that the genetic pathways of tumor progression differ in the two groups. The high frequency of germline BRCA mutations detected in this pilot study (16% of 37 invasive carcinomas) points to the need for more extended analyses of population-based series of patients to determine the true contribution of these predisposing genes to the overall incidence of ovarian cancer in this population.
Department/s
- Tumor microenvironment
- Breastcancer-genetics
- Division of Clinical Genetics
Publishing year
2000
Language
English
Pages
289-295
Publication/Series
International Journal of Gynecological Cancer
Volume
10
Issue
4
Links
Document type
Journal article
Publisher
Wiley-Blackwell
Topic
- Cancer and Oncology
Keywords
- BRCA1 • BRCA2 • chromosome 6 • cytogenetics • karyotype • ovarian cancer
Status
Published
ISBN/ISSN/Other
- ISSN: 1048-891X