BRCA1 Mutations in High-grade Serous Ovarian Cancer Are Associated with Proteomic Changes in DNA Repair, Splicing, Transcription Regulation and Signaling

Overview

Journal Sci Rep

Specialty Science

Date 2022 Mar 16

PMID 35292711

Authors

Melissa Bradbury

Eva Borras

Josep Castellvi

Olga Mendez

Jose Luis Sanchez-Iglesias

Assumpcio Perez-Benavente

Antonio Gil-Moreno

Eduard Sabido

Anna Santamaria

Affiliations

Soon will be listed here.

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.

Citing Articles

A combination of molecular and clinical parameters provides a new strategy for high-grade serous ovarian cancer patient management.

Bradbury M, Borras E, Vilar M, Castellvi J, Sanchez-Iglesias J, Perez-Benavente A J Transl Med. 2022; 20(1):611.

PMID: 36544142 PMC: 9773449. DOI: 10.1186/s12967-022-03816-7.

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