Mutational profile of esophageal cancer associated or not with chagasic megaesophagus in Brazilian patients.

• Grant number: 17/05788-6
• Support Opportunities: Scholarships abroad - Research Internship - Master's degree
• Start date: May 01, 2017
• End date: July 31, 2017
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: Adhemar Longatto Filho
• Grantee: Fernanda Franco Munari
• Supervisor: Pedro Gabriel Dias Ferreira
• Host Institution: Hospital do Câncer de Barretos. Fundação Pio XII (FP). Barretos , SP, Brazil
• Institution abroad: Universidade do Porto (UP), Portugal
• Associated to the scholarship: 15/20077-3 - High-risk HPV DNA detection and analysis of the mutational status of KRAS and PIK3CA genes and inflammatory cytokines panel in patients with esophageal cancer and megaesophagus with and without cancer, BP.MS

Abstract

Esophageal cancer (EC) is considered the eighth most common type of cancer and the sixth leading cause of death worldwide, with 80% of cases in developing countries such as Brazil. Among the risk factors for the development of esophagus' squamous cell carcinoma stands out smoking, alcohol consumption and chagasic megaesophagus (CME). The CME consists of non-harmonic opening of the upper esophageal sphincter that causes the increase of organ diameter due to ineffective esophageal propulsion and stasis that favors the development of EC. However, mutations in the KRAS and PIK3Ca genes among other genes are very important for the development and maintenance of the tumor, so it is important to study for the discovery of biomarkers that may help in the development of more effective therapeutic strategies for the prognosis and even the management of patients. From this, the present study aims evaluate the frequency and profile of mutations through bioinformatics tools and next-generation methodologies sequencing in Brazilian individuals with CE associated or not with the MEC and to compare with the global data of the mutational profile of cancer Esophagus available on The Cancer Genome Atlas (TCGA). To achieve our objectives, exome sequencing or a panel 150 oncogenes and tumor suppressor genes was performed by Illumina platform HiSeq System 2500 " platform. In the present proposal, an in-depth bioinformatics analysis of the cases will be carried out at I3S in Porto, Portugal. In addition to the bioinformatics analysis and association of sequencing results with the clinicopathological data of the patients, we will also compare our findings with the recent data from the TCGA to the CE. With this study, we intend to contribute to possible targeted treatments and improve the prognosis of patients through the identification of tumor biomarkers.