Análise de polimorfismos genéticos na região de ilhas CpG do gene SMO em amostras de carcinoma basocelular no estado da Paraíba

• Ano de defesa: 2018
• Autor(a) principal: Souza, Augusto Monteiro de
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal da Paraíba; Brasil; Biologia Celular e Molecular; Programa de Pós-Graduação em Biologia Celular e Molecular; UFPB
• Palavras-chave em Português: Câncer de pele; CpG-SNPs; Smoothened; Marcadores moleculares e DSAPS; Skin cancer; Molecular markers and DSAPS; Doenças cultaneas; Dermatologia; Carcinoma basocelular; Neoplasia cultânea; CNPQ::CIENCIAS BIOLOGICAS::BIOLOGIA GERAL
• Link de acesso: https://repositorio.ufpb.br/jspui/handle/123456789/14820

Basal Cell Carcinoma (BCC) is a cutaneous neoplasm that originates from epithelial basal cells that have lost their capacity for normal differentiation and keratinization. It is one of the most frequent types of skin tumors. BCCs are characterized by aberrant regulation of the Sonic Hedgehog pathway, typically through the loss of the PTCH1 receptor and activation of the SMO receptor, resulting in the deregulation of the processes involved in cell growth and proliferation. The change in the Hedgehog cell-signaling pathway has been detected in many human cancers, being deregulated in more than 30% of human cancers, including BCC, medulloblastoma (MB), melanoma, breast, prostate, lung, pancreas, cervical and cervical cancer. SNPs (Single Base Nucleotide Polymorphism) occur frequently in the population, such variations in the genome may be the subject of study as susceptible to disease susceptibility, including cancer. Studies have associated a number of SNPs in promoters associated with gene silencing induced by methylation in various types of cancers. SNPs on the CpG islands located in gene promoter regions are proposed as being associated with multiple diseases. The objective of this study was to perform genotyping of SNPs in the promoter region of the SMO gene in BCC samples and to determine if there is an association of these SNPs of the gene in question with the susceptibility to the development of BCC. One hundred samples of paraffined tissue from patients from the State of Paraíba with histopathological diagnosis of BCC were analyzed for each polymorphism. The results were obtained by DSASP - Dideoxy Single Allele - Specific PCR (Dideoxy Single Allele Specific - PCR). The software Bioestat - version 5.3 and Haploview 4.2 were used for the statistical analysis and application of Chi-square test and Fisher's exact test, considering a level of significance 5%. The analuzes suggest that the SNP rs538312246 is Hardy-Weinberg equilibrium, therefore, it did not present significant association with BCC in the analyzed samples (X2 = 2,343 and P < 0,1258). However, the SNPs rs375350898 and rs75827493 located in the CpG Island region of the SMO gene promoter were significantly associated with BCC in the analyzed samples (X2 = 27,740/21,500 e P < 0,0001), as well as, the SNP rs75827493 showed a significant association with the BCC of the nodular subtype in the analyzed samples (P < 0,0069). Therefore, the results suggest that SNPs rs375350898 and rs75827493 are potential molecular markers for BCC susceptibility.