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Eur J Cancer. 2014 Aug;50(12):2090-8. doi: 10.1016/j.ejca.2014.05.001. Epub 2014 Jun 2.

BRCA1 gene promoter methylation status in high-grade serous ovarian cancer patients--a study of the tumour Bank ovarian cancer (TOC) and ovarian cancer diagnosis consortium (OVCAD).

Author information

1
Department of Gynecology, European Competence Center for Ovarian Cancer, Campus Virchow Klinikum, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, D-13353 Berlin, Germany; Department of Gynecology, Obstetrics and Urology, Sapienza University of Rome, Rome, Italy.
2
Department of Gynecology, European Competence Center for Ovarian Cancer, Campus Virchow Klinikum, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, D-13353 Berlin, Germany.
3
Ivana Türbachova Laboratory for Epigenetics, Epiontis GMBH, Berlin, Germany.
4
Department of Gynecology, Obstetrics and Urology, Sapienza University of Rome, Rome, Italy.
5
Department of Obstetrics and Gynecology, Molecular Oncology Group, Comprehensive Cancer Center, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
6
Division of Gynaecological Oncology, Department of Obstetrics and Gynaecology, Universitaire Ziekenhuizen Leuven, Katholieke Universiteit Leuven, UZ Leuven, Herestraat 49, B-3000 Leuven, Belgium.
7
Department of Gynecology and Gynecologic Oncology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, D-20246 Hamburg, Germany.
8
Department of Gynecology and Obstetrics, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria.
9
Institute of Pathology, Charite Medical University, Berlin, Campus Mitte, Germany.
10
Department of Gynecology, European Competence Center for Ovarian Cancer, Campus Virchow Klinikum, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, D-13353 Berlin, Germany. Electronic address: elena.braicu@charite.de.

Abstract

BACKGROUND:

Mutations in BRCA1/2 genes are involved in the pathogenesis of breast and ovarian cancer. Inactivation of these genes can also be mediated by hypermethylation of CpGs in the promoter regions. Aim of this study was to analyse the clinical impact of BRCA1 promoter gene methylation status in a homogenous cohort of high-grade serous ovarian cancer (HGSOC) patients.

METHODS:

The cohort included 257 primary HGSOC patients treated by cytoreduction and platinum-based chemotherapy. DNA was extracted from fresh frozen tissue samples. BRCA1 gene promoter methylation rate was assessed using polymerase chain reaction (PCR).

RESULTS:

14.8% of patients presented hypermethylation within a selected region of the BRCA1 promoter. The rate of hypermethylation was significantly higher in younger patients (20.8% hypermethylation in the age group ⩽ 58 years versus 8.7% hypermethylation in the age group >58 years; p = 0.008). Optimal tumour debulking could be reached in 63% of patients, without significant differences in the extent of residual disease with respect to the methylation status. No impact of BRCA1 gene promoter methylation status on progression free- and overall-survival rates was found. No significant differences within BRCA1 promoter methylation status between primary and metastatic tissue could be observed. These results on BRCA1 promoter methylation status were also confirmed in a subgroup of 107 patients found negative for BRCA1 exon 11 mutations.

CONCLUSIONS:

Our data suggest that BRCA1 methylation determines the earlier onset of HGSOC. Furthermore our study supports the idea that BRCAness is not only due to mutations but also to epigenetic changes in BRCA1 promoter gene.

KEYWORDS:

BRCA1; Gene promoter; High grade serous ovarian cancer; Methylation; Prognosis

PMID:
24889916
DOI:
10.1016/j.ejca.2014.05.001
[Indexed for MEDLINE]

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