Análise da associação de SNPs nos genes MSH2 E MSH6 à susceptibilidade ao desenvolvimento do Carcinoma Basocelular no Estado da Paraíba
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações da UFPB |
Texto Completo: | https://repositorio.ufpb.br/jspui/handle/123456789/15394 |
Resumo: | Basal Cell Carcinoma (BCC) is a cutaneous neoplasm characterized by the presence of cancer cells, which originate from the cells of the epidermis, preventing cell differentiation and affecting the cutaneous attachments. Its main development factor is exposure to solar radiation, causing DNA damage. In response to the damage, repair mechanisms such as the mismatch repair mechanism (MMR) are used to maintain genomic integrity. The presence of single nucleotide polymorphism (SNP) in MMR genes can promote changes in the activity of its gene product, leading to tumor progression and câncer. The present study analyzed the SNPs rs63751445 (A> G) and rs63751089 (T> C) in the MSH2 gene and rs863224614 (T> G) in the MSH6 gene, in 100 paraffin tissue samples from patients diagnosed with CBC in Paraíba. The results of the analyzes were obtained by the genotyping method Didesoxi Single Allele Specific PCR - DSASP. Bioestat software was used for the statistical analyzes, which consisted of Chi-square and Fisher Exact tests, with a significance level of 5%. Molecular anchoring tests (Docking) were performed in the Hex 8.0.0 software, for analyzes of the complexes, with the Pymol and the software WinCoot 0.8.4 was used. The observed and expected genotype frequency relation in the SNPs rs63751445, rs63751089 in the MSH2 gene and the rs863224614 SNP in the MSH6 gene indicate Hardy-Weinberg imbalance with X² = 100 and p-value <0.0001 associated with susceptibility to Basal Cell Carcinoma. The anchoring allowed to identify important interactions, wherein the substitution of Phenylalanine for Leucine the interaction with DG24 is lost, suggesting the compromise of the protein function. With a statistically significant association with susceptibility to the risk of developing BCC, the results obtained may be used as molecular marker potentials. |
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Biblioteca Digital de Teses e Dissertações da UFPB |
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Análise da associação de SNPs nos genes MSH2 E MSH6 à susceptibilidade ao desenvolvimento do Carcinoma Basocelular no Estado da ParaíbaCarcinoma BasocelularMSH2MSH6SNPsDSASPBasal Cell CarcinomaDSASPCâncerCarcinoma basocelular - Diagnósticos - ParaíbaGene MSH2Gene MSH6CNPQ::CIENCIAS BIOLOGICAS::BIOLOGIA GERALBasal Cell Carcinoma (BCC) is a cutaneous neoplasm characterized by the presence of cancer cells, which originate from the cells of the epidermis, preventing cell differentiation and affecting the cutaneous attachments. Its main development factor is exposure to solar radiation, causing DNA damage. In response to the damage, repair mechanisms such as the mismatch repair mechanism (MMR) are used to maintain genomic integrity. The presence of single nucleotide polymorphism (SNP) in MMR genes can promote changes in the activity of its gene product, leading to tumor progression and câncer. The present study analyzed the SNPs rs63751445 (A> G) and rs63751089 (T> C) in the MSH2 gene and rs863224614 (T> G) in the MSH6 gene, in 100 paraffin tissue samples from patients diagnosed with CBC in Paraíba. The results of the analyzes were obtained by the genotyping method Didesoxi Single Allele Specific PCR - DSASP. Bioestat software was used for the statistical analyzes, which consisted of Chi-square and Fisher Exact tests, with a significance level of 5%. Molecular anchoring tests (Docking) were performed in the Hex 8.0.0 software, for analyzes of the complexes, with the Pymol and the software WinCoot 0.8.4 was used. The observed and expected genotype frequency relation in the SNPs rs63751445, rs63751089 in the MSH2 gene and the rs863224614 SNP in the MSH6 gene indicate Hardy-Weinberg imbalance with X² = 100 and p-value <0.0001 associated with susceptibility to Basal Cell Carcinoma. The anchoring allowed to identify important interactions, wherein the substitution of Phenylalanine for Leucine the interaction with DG24 is lost, suggesting the compromise of the protein function. With a statistically significant association with susceptibility to the risk of developing BCC, the results obtained may be used as molecular marker potentials.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESO Carcinoma Basocelular (CBC) é uma neoplasia cutânea caracterizada pela presença de células cancerosas, que se originam das células basais da epiderme, impedindo a diferenciação celular e acometendo os anexos cutâneos. Seu principal fator de desenvolvimento é a exposição à radiação solar, causando danos direto ao DNA. Em resposta aos danos, mecanismos de reparos como o Mecanismo de Reparo de Mal Pareamento (MMR) são utilizados para manter a integridade genômica. A presença de Polimorfismo de Nucleotídeo Único (SNP) em genes do MMR podem promover alterações na atividade de seu produto gênico, levando a progressão tumoral e surgimento do câncer. O presente trabalho analisou os SNPs rs63751445 (A>G) e rs63751089 (T>C) no gene MSH2 e rs863224614 (T>G) no gene MSH6, em 100 amostras de tecido parafinado de pacientes diagnosticados com CBC no estado da Paraíba. Os resultados das análises foram obtidos pelo método de genotipagem Didesoxi Único Alelo Específico PCR – DSASP. O software Bioestat foi utilizado para as análises estatísticas, que consistiram nos testes Qui-quadrado e Exato de Fisher, com nível de significância de 5%. Os testes de ancoragem molecular (Docking) foram realizados no software Hex 8.0.0, para análises dos complexos utilizou-se o Pymol e o software WinCoot 0.8.4. A relação da frequência genotípica observada e esperada nos SNPs rs63751445, rs63751089 no gene MSH2 e o SNP rs863224614 no gene MSH6 indicam desequilíbrio de Hardy-Weinberg com o X² = 100 e p-valor < 0,0001 associados a susceptibilidade ao Carcinoma Basocelular. A ancoragem permitiu identificar interações importantes, onde na substituição da Fenilalanina por Leucina a interação com DG24 é perdida, sugerindo o compromentimento da função proteica. Apresentando associação estatisticamente significativa à susceptibilidade ao risco de desenvolver CBC, os resultados obtidos poderão ser utilizados como potencias marcadores moleculares.Universidade Federal da ParaíbaBrasilBiologia Celular e MolecularPrograma de Pós-Graduação em Biologia Celular e MolecularUFPBDelatorre, Plíniohttp://lattes.cnpq.br/7961149719224268Lima, Eleonidas Mourahttp://lattes.cnpq.br/5494251269749692Liberato, Andressa de Lima2019-08-27T14:22:09Z2018-02-142019-08-27T14:22:09Z2018-12-13info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesishttps://repositorio.ufpb.br/jspui/handle/123456789/15394porAttribution-NoDerivs 3.0 Brazilhttp://creativecommons.org/licenses/by-nd/3.0/br/info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UFPBinstname:Universidade Federal da Paraíba (UFPB)instacron:UFPB2019-08-27T14:22:09Zoai:repositorio.ufpb.br:123456789/15394Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufpb.br/PUBhttp://tede.biblioteca.ufpb.br:8080/oai/requestdiretoria@ufpb.br|| diretoria@ufpb.bropendoar:2019-08-27T14:22:09Biblioteca Digital de Teses e Dissertações da UFPB - Universidade Federal da Paraíba (UFPB)false |
dc.title.none.fl_str_mv |
Análise da associação de SNPs nos genes MSH2 E MSH6 à susceptibilidade ao desenvolvimento do Carcinoma Basocelular no Estado da Paraíba |
title |
Análise da associação de SNPs nos genes MSH2 E MSH6 à susceptibilidade ao desenvolvimento do Carcinoma Basocelular no Estado da Paraíba |
spellingShingle |
Análise da associação de SNPs nos genes MSH2 E MSH6 à susceptibilidade ao desenvolvimento do Carcinoma Basocelular no Estado da Paraíba Liberato, Andressa de Lima Carcinoma Basocelular MSH2 MSH6 SNPs DSASP Basal Cell Carcinoma DSASP Câncer Carcinoma basocelular - Diagnósticos - Paraíba Gene MSH2 Gene MSH6 CNPQ::CIENCIAS BIOLOGICAS::BIOLOGIA GERAL |
title_short |
Análise da associação de SNPs nos genes MSH2 E MSH6 à susceptibilidade ao desenvolvimento do Carcinoma Basocelular no Estado da Paraíba |
title_full |
Análise da associação de SNPs nos genes MSH2 E MSH6 à susceptibilidade ao desenvolvimento do Carcinoma Basocelular no Estado da Paraíba |
title_fullStr |
Análise da associação de SNPs nos genes MSH2 E MSH6 à susceptibilidade ao desenvolvimento do Carcinoma Basocelular no Estado da Paraíba |
title_full_unstemmed |
Análise da associação de SNPs nos genes MSH2 E MSH6 à susceptibilidade ao desenvolvimento do Carcinoma Basocelular no Estado da Paraíba |
title_sort |
Análise da associação de SNPs nos genes MSH2 E MSH6 à susceptibilidade ao desenvolvimento do Carcinoma Basocelular no Estado da Paraíba |
author |
Liberato, Andressa de Lima |
author_facet |
Liberato, Andressa de Lima |
author_role |
author |
dc.contributor.none.fl_str_mv |
Delatorre, Plínio http://lattes.cnpq.br/7961149719224268 Lima, Eleonidas Moura http://lattes.cnpq.br/5494251269749692 |
dc.contributor.author.fl_str_mv |
Liberato, Andressa de Lima |
dc.subject.por.fl_str_mv |
Carcinoma Basocelular MSH2 MSH6 SNPs DSASP Basal Cell Carcinoma DSASP Câncer Carcinoma basocelular - Diagnósticos - Paraíba Gene MSH2 Gene MSH6 CNPQ::CIENCIAS BIOLOGICAS::BIOLOGIA GERAL |
topic |
Carcinoma Basocelular MSH2 MSH6 SNPs DSASP Basal Cell Carcinoma DSASP Câncer Carcinoma basocelular - Diagnósticos - Paraíba Gene MSH2 Gene MSH6 CNPQ::CIENCIAS BIOLOGICAS::BIOLOGIA GERAL |
description |
Basal Cell Carcinoma (BCC) is a cutaneous neoplasm characterized by the presence of cancer cells, which originate from the cells of the epidermis, preventing cell differentiation and affecting the cutaneous attachments. Its main development factor is exposure to solar radiation, causing DNA damage. In response to the damage, repair mechanisms such as the mismatch repair mechanism (MMR) are used to maintain genomic integrity. The presence of single nucleotide polymorphism (SNP) in MMR genes can promote changes in the activity of its gene product, leading to tumor progression and câncer. The present study analyzed the SNPs rs63751445 (A> G) and rs63751089 (T> C) in the MSH2 gene and rs863224614 (T> G) in the MSH6 gene, in 100 paraffin tissue samples from patients diagnosed with CBC in Paraíba. The results of the analyzes were obtained by the genotyping method Didesoxi Single Allele Specific PCR - DSASP. Bioestat software was used for the statistical analyzes, which consisted of Chi-square and Fisher Exact tests, with a significance level of 5%. Molecular anchoring tests (Docking) were performed in the Hex 8.0.0 software, for analyzes of the complexes, with the Pymol and the software WinCoot 0.8.4 was used. The observed and expected genotype frequency relation in the SNPs rs63751445, rs63751089 in the MSH2 gene and the rs863224614 SNP in the MSH6 gene indicate Hardy-Weinberg imbalance with X² = 100 and p-value <0.0001 associated with susceptibility to Basal Cell Carcinoma. The anchoring allowed to identify important interactions, wherein the substitution of Phenylalanine for Leucine the interaction with DG24 is lost, suggesting the compromise of the protein function. With a statistically significant association with susceptibility to the risk of developing BCC, the results obtained may be used as molecular marker potentials. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018-02-14 2018-12-13 2019-08-27T14:22:09Z 2019-08-27T14:22:09Z |
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 |
https://repositorio.ufpb.br/jspui/handle/123456789/15394 |
url |
https://repositorio.ufpb.br/jspui/handle/123456789/15394 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
Attribution-NoDerivs 3.0 Brazil http://creativecommons.org/licenses/by-nd/3.0/br/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Attribution-NoDerivs 3.0 Brazil http://creativecommons.org/licenses/by-nd/3.0/br/ |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Universidade Federal da Paraíba Brasil Biologia Celular e Molecular Programa de Pós-Graduação em Biologia Celular e Molecular UFPB |
publisher.none.fl_str_mv |
Universidade Federal da Paraíba Brasil Biologia Celular e Molecular Programa de Pós-Graduação em Biologia Celular e Molecular UFPB |
dc.source.none.fl_str_mv |
reponame:Biblioteca Digital de Teses e Dissertações da UFPB instname:Universidade Federal da Paraíba (UFPB) instacron:UFPB |
instname_str |
Universidade Federal da Paraíba (UFPB) |
instacron_str |
UFPB |
institution |
UFPB |
reponame_str |
Biblioteca Digital de Teses e Dissertações da UFPB |
collection |
Biblioteca Digital de Teses e Dissertações da UFPB |
repository.name.fl_str_mv |
Biblioteca Digital de Teses e Dissertações da UFPB - Universidade Federal da Paraíba (UFPB) |
repository.mail.fl_str_mv |
diretoria@ufpb.br|| diretoria@ufpb.br |
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1801842953251979264 |