Expression profiling in ovarian cancer reveals coordinated regulation of BRCA1/2 and homologous recombination genes
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2022 |
| Outros Autores: | , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | http://hdl.handle.net/10451/55077 |
Resumo: | © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
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Expression profiling in ovarian cancer reveals coordinated regulation of BRCA1/2 and homologous recombination genesOvarian cancerBRCA1/2 mRNAHomologous recombinationnCounter assayddPCR© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).Predictive biomarkers are crucial in clarifying the best strategy to use poly(ADP-ribose) polymerase inhibitors (PARPi) for the greatest benefit to ovarian cancer patients. PARPi are specifically lethal to cancer cells that cannot repair DNA damage by homologous recombination (HR), and HR deficiency is frequently associated with BRCA1/2 mutations. Genetic tests for BRCA1/2 mutations are currently used in the clinic, but results can be inconclusive due to the high prevalence of rare DNA sequence variants of unknown significance. Most tests also fail to detect epigenetic modifications and mutations located deep within introns that may alter the mRNA. The aim of this study was to investigate whether quantitation of BRCA1/2 mRNAs in ovarian cancer can provide information beyond the DNA tests. Using the nCounter assay from NanoString Technologies, we analyzed RNA isolated from 38 ovarian cancer specimens and 11 normal fallopian tube samples. We found that BRCA1/2 expression was highly variable among tumors. We further observed that tumors with lower levels of BRCA1/2 mRNA showed downregulated expression of 12 additional HR genes. Analysis of 299 ovarian cancer samples from The Cancer Genome Atlas (TCGA) confirmed the coordinated expression of BRCA1/2 and HR genes. To facilitate the routine analysis of BRCA1/2 mRNA in the clinical setting, we developed a targeted droplet digital PCR approach that can be used with FFPE samples. In conclusion, this study underscores the potential clinical benefit of measuring mRNA levels in tumors when BRCA1/2 DNA tests are negative or inconclusive.This research was funded by the Fundação para a Ciência e a Tecnologia, Portugal (PTDC/MED-ONC/29469/2017) and an unrestricted grant from AstraZeneca to M.C.-F. R.S. was a recipient of an EMBO Long-Term Fellowship (EMBO ALTF 101-2019). This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 842695.MDPIRepositório da Universidade de LisboaCustódio, NoéliaSavisaar, RosinaCarvalho, CéliaBak-Gordon, PedroRibeiro, Maria I.Almeida-Tavares, JoanaNunes, Paula B.Peixoto, CarolinaPinto, CarlaEscudeiro, CarlaTeixeira, Manuel R.Carmo-Fonseca, Maria2022-11-11T16:35:38Z20222022-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/55077engBiomedicines 2022, 10(2), 19910.3390/biomedicines100201992227-9059info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-11-20T18:17:39Zoai:repositorio.ul.pt:10451/55077Portal AgregadorONGhttps://www.rcaap.pt/oai/openairemluisa.alvim@gmail.comopendoar:71602024-11-20T18:17:39Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
| dc.title.none.fl_str_mv |
Expression profiling in ovarian cancer reveals coordinated regulation of BRCA1/2 and homologous recombination genes |
| title |
Expression profiling in ovarian cancer reveals coordinated regulation of BRCA1/2 and homologous recombination genes |
| spellingShingle |
Expression profiling in ovarian cancer reveals coordinated regulation of BRCA1/2 and homologous recombination genes Custódio, Noélia Ovarian cancer BRCA1/2 mRNA Homologous recombination nCounter assay ddPCR |
| title_short |
Expression profiling in ovarian cancer reveals coordinated regulation of BRCA1/2 and homologous recombination genes |
| title_full |
Expression profiling in ovarian cancer reveals coordinated regulation of BRCA1/2 and homologous recombination genes |
| title_fullStr |
Expression profiling in ovarian cancer reveals coordinated regulation of BRCA1/2 and homologous recombination genes |
| title_full_unstemmed |
Expression profiling in ovarian cancer reveals coordinated regulation of BRCA1/2 and homologous recombination genes |
| title_sort |
Expression profiling in ovarian cancer reveals coordinated regulation of BRCA1/2 and homologous recombination genes |
| author |
Custódio, Noélia |
| author_facet |
Custódio, Noélia Savisaar, Rosina Carvalho, Célia Bak-Gordon, Pedro Ribeiro, Maria I. Almeida-Tavares, Joana Nunes, Paula B. Peixoto, Carolina Pinto, Carla Escudeiro, Carla Teixeira, Manuel R. Carmo-Fonseca, Maria |
| author_role |
author |
| author2 |
Savisaar, Rosina Carvalho, Célia Bak-Gordon, Pedro Ribeiro, Maria I. Almeida-Tavares, Joana Nunes, Paula B. Peixoto, Carolina Pinto, Carla Escudeiro, Carla Teixeira, Manuel R. Carmo-Fonseca, Maria |
| author2_role |
author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
| dc.contributor.author.fl_str_mv |
Custódio, Noélia Savisaar, Rosina Carvalho, Célia Bak-Gordon, Pedro Ribeiro, Maria I. Almeida-Tavares, Joana Nunes, Paula B. Peixoto, Carolina Pinto, Carla Escudeiro, Carla Teixeira, Manuel R. Carmo-Fonseca, Maria |
| dc.subject.por.fl_str_mv |
Ovarian cancer BRCA1/2 mRNA Homologous recombination nCounter assay ddPCR |
| topic |
Ovarian cancer BRCA1/2 mRNA Homologous recombination nCounter assay ddPCR |
| description |
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
| publishDate |
2022 |
| dc.date.none.fl_str_mv |
2022-11-11T16:35:38Z 2022 2022-01-01T00:00:00Z |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
| dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
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article |
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publishedVersion |
| dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10451/55077 |
| url |
http://hdl.handle.net/10451/55077 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
Biomedicines 2022, 10(2), 199 10.3390/biomedicines10020199 2227-9059 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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MDPI |
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MDPI |
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reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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mluisa.alvim@gmail.com |
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1817549208954077184 |