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

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

JOURNAL=Frontiers in Oncology

VOLUME=Volume 13 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1268127

DOI=10.3389/fonc.2023.1268127

ISSN=2234-943X

ABSTRACT=<sec><title>Introduction</title><p><italic>BRCA1</italic> methylated (<italic>BRCA1<sup>met</sup></italic>) 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 <italic>BRCA1<sup>met</sup></italic> cases, and, as a matter of fact, we still do not know if this subset of EOCs is similar, and to what extent, to <italic>BRCA1</italic> mutated (<italic>BRCA1<sup>mut</sup></italic>) cases.</p></sec><sec><title>Methods</title><p>We compared a group of 17 <italic>BRCA1<sup>met</sup></italic> cases against 10 <italic>BRCA1<sup>mut</sup></italic> cases using a subset of carefully selected 17 <italic>BRCA<sup>wt</sup></italic> EOCs as a control group.</p></sec><sec><title>Results</title><p>First, <italic>BRCA1<sup>met</sup></italic> cases showed a downregulation of the relative transcript, while this association was not observed for <italic>BRCA1<sup>mut</sup></italic> EOCs. The <italic>BRCA1<sup>met</sup></italic> group exhibited a general upregulation of homologous recombination (HR)-related genes, as well as <italic>BRCA1<sup>mut</sup></italic>. Overall, <italic>BRCA1<sup>met</sup></italic> had a different gene expression profile, characterized by diffuse downregulation, whereas <italic>BRCA1<sup>mut</sup></italic> showed a general upregulation (p &lt; 0.0001). Both <italic>BRCA1</italic>-defective groups showed a slightly activated immune response mediated by interferon (IFN) gamma pathways.</p></sec><sec><title>Discussion</title><p>In conclusion, even if the expression profile of many genes related to DNA damage and repair system is shared between <italic>BRCA1<sup>mut</sup></italic> and <italic>BRCA1<sup>met</sup></italic> EOCs supporting that <italic>BRCA1<sup>met</sup></italic> EOCs may benefit from PARPi therapies, our data demonstrate that <italic>BRCA1<sup>mut</sup></italic> and <italic>BRCA1<sup>met</sup></italic> EOCs show different expression profiles, suggesting a different mechanism of carcinogenesis that can be reflected in different responses to therapies and disease recovery.</p></sec>