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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  • dc.contributor.author Bradbury Lobato, Melissa, 1983-
  • dc.contributor.author Borràs, Eva
  • dc.contributor.author Castellví, Josep
  • dc.contributor.author Méndez, Olga
  • dc.contributor.author Sánchez-Iglesias, José Luis
  • dc.contributor.author Pérez-Benavente, Assumpció
  • dc.contributor.author Gil-Moreno, Antonio
  • dc.contributor.author Sabidó Aguadé, Eduard, 1981-
  • dc.contributor.author Santamaria, Anna
  • dc.date.accessioned 2022-06-01T08:57:22Z
  • dc.date.available 2022-06-01T08:57:22Z
  • dc.date.issued 2022
  • dc.description.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.
  • dc.description.sponsorship This work was supported by the PhD4MD collaborative research program between the Vall d’Hebron Research Institute (VHIR) and the Centre for Genomic Regulation (CRG). The CRG/UPF Proteomics Unit is part of the Spanish Infrastructure for Omics Technologies (ICTS OmicsTech) and it is a member of the ProteoRed PRB3 consortium which is supported by grant PT17/0019 of the PE I+D+i 2013-2016 from the Instituto de Salud Carlos III (ISCIII) and ERDF. We acknowledge support from the Spanish Ministry of Science, Innovation and Universities, (CTQ2016-80364-P and “Centro de Excelencia Severo Ochoa 2013-2017”, SEV-2012-0208), and “Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement de la Generalitat de Catalunya” (2017SGR595 and 2017SGR1661). This project has also received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 823839 (EPIC-XS). It has also been supported by grants from the Instituto Carlos III (PI15/00238, PI18/01017, PI21/00977), the Miguel Servet Program (CP13/00158 and CPII18/00027) and the Ministerio de Economía y Competitividad y Fondos FEDER (RTC-2015-3821-1)
  • dc.format.mimetype application/pdf
  • dc.identifier.citation 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
  • dc.identifier.doi http://dx.doi.org/10.1038/s41598-022-08461-0
  • dc.identifier.issn 2045-2322
  • dc.identifier.uri http://hdl.handle.net/10230/53343
  • dc.language.iso eng
  • dc.publisher Nature Research
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/823839
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/CTQ2016-80364-P
  • dc.rights © Melissa Bradbury et al 2022. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri https://creativecommons.org/licenses/by/4.0/
  • dc.subject.other Ovaris -- Càncer
  • dc.subject.other Genòmica
  • dc.subject.other Genètica
  • dc.title BRCA1 mutations in high-grade serous ovarian cancer are associated with proteomic changes in DNA repair, splicing, transcription regulation and signaling
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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