BRCA1 mutations in high-grade serous ovarian cancer are associated with proteomic changes in DNA repair, splicing, transcription regulation and signaling

Bradbury Lobato, Melissa, 1983-; Borràs, Eva; Castellví, Josep; Méndez, Olga; Sánchez-Iglesias, José Luis; Pérez-Benavente, Assumpció; Gil-Moreno, Antonio; Sabidó Aguadé, Eduard, 1981-; Santamaria, Anna

doi:http://dx.doi.org/10.1038/s41598-022-08461-0

BRCA1 mutations in high-grade serous ovarian cancer are associated with proteomic changes in DNA repair, splicing, transcription regulation and signaling

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Bradbury M, Borràs E, Castellví J, Méndez O, Sánchez-Iglesias, JL et al. BRCA1 mutations in high-grade serous ovarian cancer are associated with proteomic changes in DNA repair, splicing, transcription regulation and signaling. Sci Rep. 2022 Mar 15;12(1):4445. DOI:10.1038/s41598-022-08461-0

Abstract

Despite recent advances in the management of BRCA1 mutated high-grade serous ovarian cancer (HGSC), the physiology of these tumors remains poorly understood. Here we provide a comprehensive molecular understanding of the signaling processes that drive HGSC pathogenesis with the addition of valuable ubiquitination profiling, and their dependency on BRCA1 mutation-state directly in patient-derived tissues. Using a multilayered proteomic approach, we show the tight coordination between the ubiquitination and phosphorylation regulatory layers and their role in key cellular processes related to BRCA1-dependent HGSC pathogenesis. In addition, we identify key bridging proteins, kinase activity, and post-translational modifications responsible for molding distinct cancer phenotypes, thus providing new opportunities for therapeutic intervention, and ultimately advance towards a more personalized patient care.