Using Whole Exome Sequencing on Diagnosis of Pancreatic Ductal Adenocarcinoma

• Autor(a) principal: Bernardes, Jacques de Oliveira
• Data de Publicação: 2023
• Outros Autores: Toledo-Silva, Guilherme
• Tipo de documento: Artigo
• Idioma: por
• Título da fonte: Revista Brasileira de Cancerologia (Online)
• Texto Completo: https://rbc.inca.gov.br/index.php/revista/article/view/3006
• topic: carcinoma ductal pancreático; sequenciamento completo do exoma; terapia de alvo molecular; carcinoma, pancreatic ductal; whole exome sequencing; molecular targeted therapy; carcinoma ductal pancreático; secuenciación del exoma completo; terapia molecular dirigida

Introduction: The prevalence of pancreatic ductal adenocarcinoma (PDAC) in Brazil is around two percent of all neoplasms. It is an aggressive disease responsible for five percent of all deaths by cancer. The analysis of exome – part of the DNA encoding the proteins – allows the identification of tumor-specific variants and the patient polymorphism. This information is necessary to implement target therapy for PDAC, as it provides evidence to select, or exclude, PDAC treatments. Objective: Identify the somatic and germinative variants of clinical and pharmacological interest in the PDAC for four patients through the whole-exome sequencing technique (WES). Method: Public sequencing exome data published by Texas Cancer Research Biobank were utilized, from four tumor-normal samples pair of PDAC located in the pancreas head of Caucasian patients, T3N1M0 stage. To identify somatic and germinative variations, the GATK software was adopted. Furthermore, these variants were noted with their clinical and pharmacological information through the VEP software and its consequences were analyzed through the statistical software R. Results: Of the four tumors, one has a structural variant with duplication of the AKT2 gene; another, changes in the pathway of cyclins CDK14 and CDKN2C. Both findings alter the chemotherapy regimen; in the germline, one patient has variants in the XRCC1 gene, which suggests increased response to platinum. Conclusion: Although the pathology classifies all tumours as PDAC, each patient – as well as their respective tumor – shows specificities that affect the diagnosis and therapeutic possibilities. WES allows to identify them at a low cost, expanding the treatment possibilities of PDAC.