O Uso do Sequenciamento Total do Exoma no Diagnóstico do Adenocarcinoma Ductal Pancreático

Autores

  • Jacques de Oliveira Bernardes Universidade Federal de Santa Catarina (UFSC). Departamento de Biologia Celular, Embriologia e Genética. Florianópolis (SC), Brasil. https://orcid.org/0000-0002-5162-5444
  • Guilherme Toledo-Silva Universidade Federal de Santa Catarina (UFSC). Departamento de Biologia Celular, Embriologia e Genética. Florianópolis (SC), Brasil. https://orcid.org/0000-0002-9953-2861

DOI:

https://doi.org/10.32635/2176-9745.RBC.2023v69n1.3006

Palavras-chave:

carcinoma ductal pancreático, sequenciamento completo do exoma, terapia de alvo molecular

Resumo

 

Introdução: O adenocarcinoma ductal pancreático (PDAC) é uma doença agressiva responsável no Brasil por 2% das neoplasias e 5% das mortes por câncer. A análise do exoma – parte do DNA que codifica as proteínas – permite identificar as variantes somáticas do tumor e as germinativas do paciente. Essa informação é necessária para implementar a terapia-alvo para o PDAC, pois fornece evidência para selecionar, ou excluir, tratamentos para a doença. Objetivo: Identificar as variantes de interesse clínico e farmacológico presentes no PDAC de quatro pacientes, por meio da técnica de sequenciamento total do exoma (WES). Método: Foram utilizados dados públicos de quatro amostras de pares tumor-normal de PDAC, localizados na cabeça do pâncreas de pacientes caucasianos, estádio T3N1M0, sequenciadas e publicizadas pelo Texas Cancer Research Biobank. Para identificar as variações somáticas e germinativas, utilizou-se o software GATK. As consequências clínicas e farmacológicas dessas variações foram anotadas por meio do software VEP e analisadas mediante o software estatístico R. Resultados: Dos quatro tumores, um possui variante estrutural com duplicação do gene AKT2; outro, variantes nos genes da via das ciclinas CDK14 e CDKN2C, o que altera o regime quimioterápico; na linhagem germinativa, um paciente tem variantes no gene XRCC1, que sugere aumento da resposta à platina. Conclusão: Embora a patologia classifique todos os tumores como PDAC, cada paciente – bem como o respectivo tumor – apresenta especificidades que afetam o diagnóstico e as possibilidades terapêuticas. O WES permite identificá-las a um custo baixo, o que amplia as possibilidades de tratamento do PDAC.

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Publicado

2023-01-16

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1.
Bernardes J de O, Toledo-Silva G. O Uso do Sequenciamento Total do Exoma no Diagnóstico do Adenocarcinoma Ductal Pancreático. Rev. Bras. Cancerol. [Internet]. 16º de janeiro de 2023 [citado 1º de fevereiro de 2023];69(1):e-053006. Disponível em: https://rbc.inca.gov.br/index.php/revista/article/view/3006

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