Espectro de mutações em genes associados ao adenocarcinoma de pâncreas em pacientes do sudeste brasileiro

• Ano de defesa: 2013
• Autor(a) principal: Nayra Soares do Amaral
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; UFMG
• Palavras-chave em Português: Adenocarcinoma pancreático; Ancestralidade genômica; PIK3CA; K-ras; CDKN2A; Mutações; BRAF; EGFR; P53; Adenocarcinoma; Genes ras/genética; Transformação celular neoplásica/genética; Neoplasias pancreáticas; Mutação; Neoplasias pancreáticas/genética; Marcadores genéticos
• Link de acesso: http://hdl.handle.net/1843/BUBD-9ERJ5Y

Introduction: Adenocarcinoma is the most prevalent histological type among tumors of the pancreas ( 90 % ) and has high mortality. The importance of understanding the pancreatic carcinogenesis is to determine new therapeutic targets and biomarkers to assist in early diagnosis. The progression of pancreatic ductal adenocarcinoma involved the accumulation of mutations in pre- cancerous lesions, for example, the pancreatic intraepithelial neoplasia ( PanIN ) . Molecular alterations in oncogenes such as K-ras, EGFR , BRAF , PIK3CA and loss function of tumor suppressor, such as CDKN2A and p53 are involved in tumor development. Our objective was to evaluate the frequency of mutations in genes involved in cancer progression and correlate them with the clinical and genomic ancestry Material and Methods: Mutation analysis was made by direct sequencing in 23 samples with pancreatic adenocarcinoma and ancestry was analyzed using 40 biallelic indels. Results: Among all the genes, mutations in codon 12 of K - ras were the most frequent (60 %). In PIK3CA, was identified a new mutation in one patient, do not described in the literature ( M983K ). Mutations in EGFR , BRAF , PIK3CA , CDKN2A and p53 were infrequent in our study . The genomic ancestry of our patients did not differ from the control group, however, we observed that all patients with higher African ancestral component showed mutations in K - ras . Conclusion: We observed in our patients a lower frequency of mutations in K - ras in relation to most of the results already described in other countries, but closer to the Korean population , and our samples showed a lower frequency of mutations in CDKN2A and p53 in relation to other populations, reinforcing the importance of th ethnic differences in studies involving genetic alterations in patients with pancreatic adenocarcinoma . Due to the high miscegenation of the Brazilian population, it is interesting that other studies like this are done in other regions of the country, with the objective of to characterize the genetic profile of Brazilian population with pancreatic adenocarcinoma .