Similarities and differences in gene expression profiles of BRCA1 methylated and mutated epithelial ovarian cancers

Nora Sahnane; Laura Libera; Sofia Facchi; Ileana Carnevali; Susanna Ronchi; Chiara Albeni; Antonella Cromi; Jvan Casarin; Fausto Sessa; Maria Grazia Tibiletti

doi:10.3389/fonc.2023.1268127

Similarities and differences in gene expression profiles of BRCA1 methylated and mutated epithelial ovarian cancers

Front Oncol. 2023 Oct 3:13:1268127. doi: 10.3389/fonc.2023.1268127. eCollection 2023.

Authors

Nora Sahnane^{1

2}, Laura Libera^{2

3}, Sofia Facchi^{2

3}, Ileana Carnevali^{1

2}, Susanna Ronchi^{1

2}, Chiara Albeni¹, Antonella Cromi^{3

4}, Jvan Casarin^{2

3

4}, Fausto Sessa^{1

2

3}, Maria Grazia Tibiletti²

Affiliations

¹ Unit of Pathology, Azienda Socio Sanitaria Territoriale (ASST) Sette Laghi, Varese, Italy.
² Research Centre for the Study of Hereditary and Familial Tumors, University of Insubria, Varese, Italy.
³ Department of Medicine and Technological Innovation, University of Insubria, Varese, Italy.
⁴ Obstetrics and Gynaecology Department, Del Ponte Women's and Children's Hospital, Varese, Italy.

Abstract

Introduction: BRCA1 methylated (BRCA1^met) epithelial ovarian cancer (EOC) is a recently defined and not well-investigated subset of neoplasms. To date, no studies have focused on the transcriptional profiles of BRCA1^met cases, and, as a matter of fact, we still do not know if this subset of EOCs is similar, and to what extent, to BRCA1 mutated (BRCA1^mut) cases.

Methods: We compared a group of 17 BRCA1^met cases against 10 BRCA1^mut cases using a subset of carefully selected 17 BRCA^wt EOCs as a control group.

Results: First, BRCA1^met cases showed a downregulation of the relative transcript, while this association was not observed for BRCA1^mut EOCs. The BRCA1^met group exhibited a general upregulation of homologous recombination (HR)-related genes, as well as BRCA1^mut. Overall, BRCA1^met had a different gene expression profile, characterized by diffuse downregulation, whereas BRCA1^mut showed a general upregulation (p < 0.0001). Both BRCA1-defective groups showed a slightly activated immune response mediated by interferon (IFN) gamma pathways.

Discussion: In conclusion, even if the expression profile of many genes related to DNA damage and repair system is shared between BRCA1^mut and BRCA1^met EOCs supporting that BRCA1^met EOCs may benefit from PARPi therapies, our data demonstrate that BRCA1^mut and BRCA1^met EOCs show different expression profiles, suggesting a different mechanism of carcinogenesis that can be reflected in different responses to therapies and disease recovery.

Keywords: BRCA1 methylation; EOC; NanoString®; PARPi therapy; gene expression profiles.

Grants and funding

The authors declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the University of Insubria (Grant “Alessandra Tozzi” and fellowships to SF and LL). The funding sources had no role in the design and execution of the study.