Next generation sequencing of a custom gene panel to improve the diagnosis of patients with inherited predisposition to colorectal polyposis
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Tipo de documento: | Dissertação |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.22/19857 |
Resumo: | Polyposis syndromes are a group of diseases predisposing to cancer. In general, the genetic mechanisms are well established, but in recente years several pathogenic variants in emergent genes have been associated to theses phenotypes. The main goal of this study was to search for pathogenic variants in emerging genes through a customized next-generation sequencing (NGS) panel in a retrospective series of 189 individuals with a personal/family history of polyposis previously negative for pathogenic variants in the MUTYH and/or APC genes. We also aimed to complete the study of the MUTYH gene in all patients (79 cases) previously studied only for the recurrent/founder +athogenic variants. A total of 18 variants (15 different) were found in 17 patients, seven of them deleterious (six different, two of them in the same patient) and 11 (9 different) variants of uncertain significance (two of them novel). None of the 79 cases previously studied for only the reccurent pathogenic MUTYH variants presented pathogenic variants in the remaining coding regions of this gene. This study demonstrates that pathogenic variants in the emerging genes recently associated in the literature with polyposis are rare. |
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Next generation sequencing of a custom gene panel to improve the diagnosis of patients with inherited predisposition to colorectal polyposisPolyposis syndromesHereditary colorectal cancerGermline variantsNext-generation sequencingTargeted sequencingPolyposis syndromes are a group of diseases predisposing to cancer. In general, the genetic mechanisms are well established, but in recente years several pathogenic variants in emergent genes have been associated to theses phenotypes. The main goal of this study was to search for pathogenic variants in emerging genes through a customized next-generation sequencing (NGS) panel in a retrospective series of 189 individuals with a personal/family history of polyposis previously negative for pathogenic variants in the MUTYH and/or APC genes. We also aimed to complete the study of the MUTYH gene in all patients (79 cases) previously studied only for the recurrent/founder +athogenic variants. A total of 18 variants (15 different) were found in 17 patients, seven of them deleterious (six different, two of them in the same patient) and 11 (9 different) variants of uncertain significance (two of them novel). None of the 79 cases previously studied for only the reccurent pathogenic MUTYH variants presented pathogenic variants in the remaining coding regions of this gene. This study demonstrates that pathogenic variants in the emerging genes recently associated in the literature with polyposis are rare.Teixeira, Manuel António RodriguesPinto, Carla Alexandra CavacoRepositório Científico do Instituto Politécnico do PortoSilva, Miguel Ângelo Sota Porto da2022-02-10T09:02:58Z2021-09-072021-09-07T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdftext/plain; charset=utf-8http://hdl.handle.net/10400.22/19857TID:202930122enginfo: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:RCAAP2023-03-13T13:14:45Zoai:recipp.ipp.pt:10400.22/19857Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T17:39:55.721864Repositório 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 |
Next generation sequencing of a custom gene panel to improve the diagnosis of patients with inherited predisposition to colorectal polyposis |
title |
Next generation sequencing of a custom gene panel to improve the diagnosis of patients with inherited predisposition to colorectal polyposis |
spellingShingle |
Next generation sequencing of a custom gene panel to improve the diagnosis of patients with inherited predisposition to colorectal polyposis Silva, Miguel Ângelo Sota Porto da Polyposis syndromes Hereditary colorectal cancer Germline variants Next-generation sequencing Targeted sequencing |
title_short |
Next generation sequencing of a custom gene panel to improve the diagnosis of patients with inherited predisposition to colorectal polyposis |
title_full |
Next generation sequencing of a custom gene panel to improve the diagnosis of patients with inherited predisposition to colorectal polyposis |
title_fullStr |
Next generation sequencing of a custom gene panel to improve the diagnosis of patients with inherited predisposition to colorectal polyposis |
title_full_unstemmed |
Next generation sequencing of a custom gene panel to improve the diagnosis of patients with inherited predisposition to colorectal polyposis |
title_sort |
Next generation sequencing of a custom gene panel to improve the diagnosis of patients with inherited predisposition to colorectal polyposis |
author |
Silva, Miguel Ângelo Sota Porto da |
author_facet |
Silva, Miguel Ângelo Sota Porto da |
author_role |
author |
dc.contributor.none.fl_str_mv |
Teixeira, Manuel António Rodrigues Pinto, Carla Alexandra Cavaco Repositório Científico do Instituto Politécnico do Porto |
dc.contributor.author.fl_str_mv |
Silva, Miguel Ângelo Sota Porto da |
dc.subject.por.fl_str_mv |
Polyposis syndromes Hereditary colorectal cancer Germline variants Next-generation sequencing Targeted sequencing |
topic |
Polyposis syndromes Hereditary colorectal cancer Germline variants Next-generation sequencing Targeted sequencing |
description |
Polyposis syndromes are a group of diseases predisposing to cancer. In general, the genetic mechanisms are well established, but in recente years several pathogenic variants in emergent genes have been associated to theses phenotypes. The main goal of this study was to search for pathogenic variants in emerging genes through a customized next-generation sequencing (NGS) panel in a retrospective series of 189 individuals with a personal/family history of polyposis previously negative for pathogenic variants in the MUTYH and/or APC genes. We also aimed to complete the study of the MUTYH gene in all patients (79 cases) previously studied only for the recurrent/founder +athogenic variants. A total of 18 variants (15 different) were found in 17 patients, seven of them deleterious (six different, two of them in the same patient) and 11 (9 different) variants of uncertain significance (two of them novel). None of the 79 cases previously studied for only the reccurent pathogenic MUTYH variants presented pathogenic variants in the remaining coding regions of this gene. This study demonstrates that pathogenic variants in the emerging genes recently associated in the literature with polyposis are rare. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-09-07 2021-09-07T00:00:00Z 2022-02-10T09:02:58Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.22/19857 TID:202930122 |
url |
http://hdl.handle.net/10400.22/19857 |
identifier_str_mv |
TID:202930122 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf text/plain; charset=utf-8 |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
reponame_str |
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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1799131486652203008 |