High-throughput sequencing identifies 3 novel susceptibility genes for hereditary melanoma
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2020 |
| 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/10362/147802 |
Resumo: | Funding: The authors are thankful for the collaboration of all departments involved from IPOLFG, Lisboa, Portugal. F.P. received a grant from National Funds through the Foundation for Science and Technology (FCT), reference SFRH/BPD/115730/2016. The authors are thankful for the financial support to Liga Portuguesa Contra o Cancro, Núcleo Regional Sul (LPCC-NRS), IPOLFG, TVI (Televisão Independente) and iNOVA4Health Research Unit (LISBOA-01-0145-FEDER-007344), co-funded by FCT/Ministério da Ciência e do Ensino Superior, through national funds, and FEDER under the PT2020 Partnership Agreement.. |
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High-throughput sequencing identifies 3 novel susceptibility genes for hereditary melanomaCutaneous melanomaGermline mutationsHereditary melanomaWESGeneticsGenetics(clinical)SDG 3 - Good Health and Well-beingFunding: The authors are thankful for the collaboration of all departments involved from IPOLFG, Lisboa, Portugal. F.P. received a grant from National Funds through the Foundation for Science and Technology (FCT), reference SFRH/BPD/115730/2016. The authors are thankful for the financial support to Liga Portuguesa Contra o Cancro, Núcleo Regional Sul (LPCC-NRS), IPOLFG, TVI (Televisão Independente) and iNOVA4Health Research Unit (LISBOA-01-0145-FEDER-007344), co-funded by FCT/Ministério da Ciência e do Ensino Superior, through national funds, and FEDER under the PT2020 Partnership Agreement..Cutaneous melanoma is one of the most aggressive human cancers due to its high invasiveness. Germline mutations in high-risk melanoma susceptibility genes have been associated with development hereditary melanoma; however, most genetic culprits remain elusive. To unravel novel susceptibility genes for hereditary melanoma, we performed whole exome sequencing (WES) on eight patients with multiple primary melanomas, high number of nevi, and negative for high and intermediate-risk germline mutations. Thirteen new potentially pathogenic variants were identified after bioinformatics analysis and validation. CDH23, ARHGEF40, and BRD9 were identified as the most promising susceptibility genes in hereditary melanoma. In silico analysis of CDH23 and ARHGEF40 variants provided clues for altered protein structure and function associated with the identified mutations. Then, we also evaluated the clinical value of CDH23, ARHGEF40, and BRD9 expression in sporadic melanoma by using the TCGA dataset (n = 461). No differences were observed in BRD9 expression between melanoma and normal skin samples, nor with melanoma stage, whereas ARHGEF40 was found overexpressed, and CDH23 was downregulated and its loss was associated with worse survival. Altogether, these results reveal three novel genes with clinical relevance in hereditary and sporadic melanoma.Instituto de Tecnologia Química e Biológica António Xavier (ITQB)NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)RUNCampos, CatarinaFragoso, SofiaLuís, RafaelPinto, FilipeBrito, CheilaEsteves, SusanaPataco, MargaridaSantos, SidóniaMachado, PatríciaVicente, João B.Rosa, Joaninha CostaCavaco, Branca M.Moura, CecíliaPojo, Marta2023-01-18T22:14:31Z2020-042020-04-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/147802eng0920-8569PURE: 19219738https://doi.org/10.3390/genes11040403info: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:RCAAP2024-03-11T05:29:02Zoai:run.unl.pt:10362/147802Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:53:05.019945Repositório 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 |
High-throughput sequencing identifies 3 novel susceptibility genes for hereditary melanoma |
| title |
High-throughput sequencing identifies 3 novel susceptibility genes for hereditary melanoma |
| spellingShingle |
High-throughput sequencing identifies 3 novel susceptibility genes for hereditary melanoma Campos, Catarina Cutaneous melanoma Germline mutations Hereditary melanoma WES Genetics Genetics(clinical) SDG 3 - Good Health and Well-being |
| title_short |
High-throughput sequencing identifies 3 novel susceptibility genes for hereditary melanoma |
| title_full |
High-throughput sequencing identifies 3 novel susceptibility genes for hereditary melanoma |
| title_fullStr |
High-throughput sequencing identifies 3 novel susceptibility genes for hereditary melanoma |
| title_full_unstemmed |
High-throughput sequencing identifies 3 novel susceptibility genes for hereditary melanoma |
| title_sort |
High-throughput sequencing identifies 3 novel susceptibility genes for hereditary melanoma |
| author |
Campos, Catarina |
| author_facet |
Campos, Catarina Fragoso, Sofia Luís, Rafael Pinto, Filipe Brito, Cheila Esteves, Susana Pataco, Margarida Santos, Sidónia Machado, Patrícia Vicente, João B. Rosa, Joaninha Costa Cavaco, Branca M. Moura, Cecília Pojo, Marta |
| author_role |
author |
| author2 |
Fragoso, Sofia Luís, Rafael Pinto, Filipe Brito, Cheila Esteves, Susana Pataco, Margarida Santos, Sidónia Machado, Patrícia Vicente, João B. Rosa, Joaninha Costa Cavaco, Branca M. Moura, Cecília Pojo, Marta |
| author2_role |
author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Instituto de Tecnologia Química e Biológica António Xavier (ITQB) NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM) RUN |
| dc.contributor.author.fl_str_mv |
Campos, Catarina Fragoso, Sofia Luís, Rafael Pinto, Filipe Brito, Cheila Esteves, Susana Pataco, Margarida Santos, Sidónia Machado, Patrícia Vicente, João B. Rosa, Joaninha Costa Cavaco, Branca M. Moura, Cecília Pojo, Marta |
| dc.subject.por.fl_str_mv |
Cutaneous melanoma Germline mutations Hereditary melanoma WES Genetics Genetics(clinical) SDG 3 - Good Health and Well-being |
| topic |
Cutaneous melanoma Germline mutations Hereditary melanoma WES Genetics Genetics(clinical) SDG 3 - Good Health and Well-being |
| description |
Funding: The authors are thankful for the collaboration of all departments involved from IPOLFG, Lisboa, Portugal. F.P. received a grant from National Funds through the Foundation for Science and Technology (FCT), reference SFRH/BPD/115730/2016. The authors are thankful for the financial support to Liga Portuguesa Contra o Cancro, Núcleo Regional Sul (LPCC-NRS), IPOLFG, TVI (Televisão Independente) and iNOVA4Health Research Unit (LISBOA-01-0145-FEDER-007344), co-funded by FCT/Ministério da Ciência e do Ensino Superior, through national funds, and FEDER under the PT2020 Partnership Agreement.. |
| publishDate |
2020 |
| dc.date.none.fl_str_mv |
2020-04 2020-04-01T00:00:00Z 2023-01-18T22:14:31Z |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
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http://hdl.handle.net/10362/147802 |
| url |
http://hdl.handle.net/10362/147802 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
0920-8569 PURE: 19219738 https://doi.org/10.3390/genes11040403 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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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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