Prognostic value of BRCA1 promoter methylation for patients with epithelial ovarian cancer

Henri Azaïs; Simon Garinet; Louise Benoit; Julie de Jesus; Mohamed Zizi; Samuel Landman; Anne-Sophie Bats; Valérie Taly; Pierre Laurent-Puig; Hélène Blons

doi:10.1016/j.jogoh.2024.102796

Prognostic value of BRCA1 promoter methylation for patients with epithelial ovarian cancer

J Gynecol Obstet Hum Reprod. 2024 Sep;53(7):102796. doi: 10.1016/j.jogoh.2024.102796. Epub 2024 May 8.

Authors

Affiliations

¹ AP-HP (Assistance Publique des Hôpitaux de Paris), Department of Gynaecological Oncological and Breast Surgery, Georges Pompidou European Hospital, Paris, France; Paris CARPEM Cancer Institute, Université de Paris Cité, Paris, France; INSERM UMR-S 1147, University of Paris Cité, Centre de Recherche des Cordeliers, Paris, France. Electronic address: henri.azais@aphp.fr.
² Paris CARPEM Cancer Institute, Université de Paris Cité, Paris, France; INSERM UMR-S 1147, University of Paris Cité, Centre de Recherche des Cordeliers, Paris, France; AP-HP (Assistance Publique des Hôpitaux de Paris), Department of Biochemistry, Unit of Pharmacogenetics and Molecular Oncology, Georges Pompidou European Hospital, Paris, France.
³ AP-HP (Assistance Publique des Hôpitaux de Paris), Department of Gynaecological Oncological and Breast Surgery, Georges Pompidou European Hospital, Paris, France.
⁴ AP-HP (Assistance Publique des Hôpitaux de Paris), Department of Biochemistry, Unit of Pharmacogenetics and Molecular Oncology, Georges Pompidou European Hospital, Paris, France.
⁵ AP-HP (Assistance Publique des Hôpitaux de Paris), Department of Gynaecological Oncological and Breast Surgery, Georges Pompidou European Hospital, Paris, France; Paris CARPEM Cancer Institute, Université de Paris Cité, Paris, France; INSERM UMR-S 1147, University of Paris Cité, Centre de Recherche des Cordeliers, Paris, France.
⁶ AP-HP (Assistance Publique des Hôpitaux de Paris), Department of Gynaecological Oncological and Breast Surgery, Georges Pompidou European Hospital, Paris, France; Paris CARPEM Cancer Institute, Université de Paris Cité, Paris, France; INSERM UMR-S 1147, University of Paris Cité, Centre de Recherche des Cordeliers, Paris, France; AP-HP (Assistance Publique des Hôpitaux de Paris), Department of Biochemistry, Unit of Pharmacogenetics and Molecular Oncology, Georges Pompidou European Hospital, Paris, France.
⁷ Paris CARPEM Cancer Institute, Université de Paris Cité, Paris, France; INSERM UMR-S 1147, University of Paris Cité, Centre de Recherche des Cordeliers, Paris, France.

PMID: 38729429
DOI: 10.1016/j.jogoh.2024.102796

Abstract

Objective: BRCA1 promoter methylation (BRCA1pm) is suspected to alter prognosis of patients with epithelial ovarian cancer (EOC). We aimed to evaluate the prognostic impact of this epigenetic modification.

Methods: We conducted a retrospective, monocentric study from 11/2006 to 08/2018. Patients with EOC and available status concerning somatic BRCA1/2 mutation and BRCA1pm were included. Three groups were defined: patients without BRCA1/2 mutation or BRCA1pm, patients with BRCA1/2 mutation and patients with BRCA1pm. BRCA1/2 mutations were analyzed in current care settings by next-generation sequencing (NGS). BRCA1pm analysis was assessed and quantified from bisulfite converted DNAs using fluorescent methylation specific polymerase chain reaction (PCR) and fragment analysis. All patients signed a consent form and the study was authorized by a Personal Protection Committee. Descriptive statistics were used to describe groups. Multivariate analysis was performed using the logistic regression model and including the variables that could be known at the time of diagnosis and that were significant at univariate analysis. Survival was compared between the groups. Kaplan-Mayer curves were used to express the differences in survival that were compared using log rank tests.

Results: 145 patients were included: 95 (65.5 %) patients without BRCA1/2 mutation or BRCA1pm, 32 (22.1 %) patients with BRCA1/2 mutation, 18 (12.4 %) patients with BRCA1pm. Median survival was decreased in patients with BRCA1pm. Comparison of survival revealed a significant difference in overall survival (p = 0.0078) with a worse prognosis for patients with a BRCA1pm.

Conclusion: BRCA1pm in patients with EOC is an independent factor associated with a decreased overall survival.

Synopsis: BRCA1 promotor methylation in patients with epithelial ovarian cancer is an independent factor associated with a decreased overall survival.

Keywords: BRCA1 promoter methylation; Biomarker; Circulating tumor DNA; Liquid biopsy; Ovarian cancer.

MeSH terms

Adult
Aged
BRCA1 Protein* / genetics
Carcinoma, Ovarian Epithelial* / genetics
Carcinoma, Ovarian Epithelial* / mortality
DNA Methylation* / genetics
Female
Genes, BRCA1
Humans
Middle Aged
Mutation
Ovarian Neoplasms* / genetics
Ovarian Neoplasms* / mortality
Prognosis
Promoter Regions, Genetic* / genetics
Retrospective Studies

Substances

BRCA1 Protein
BRCA1 protein, human