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Molecular characterization of gastric cancer

Grant number: 20/10878-7
Support Opportunities:Regular Research Grants
Duration: November 01, 2021 - June 30, 2024
Field of knowledge:Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
Principal Investigator:Marcus Fernando Kodama Pertille Ramos
Grantee:Marcus Fernando Kodama Pertille Ramos
Host Institution: Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira (ICESP). Coordenadoria de Serviços de Saúde (CSS). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
Associated researchers: Evandro Sobroza de Mello ; Leonardo Cardili ; Marina Alessandra Pereira ; Tiago Biachi de Castria ; Ulysses Ribeiro Júnior

Abstract

Gastric cancer (GC) is a disease with worldwide distribution and high mortality rate, being the third leading cause of cancer death worldwide. In recent years, the recognition of genetic-molecular mechanisms related to the genesis and progression of stomach neoplasms has allowed new methods of diagnosis and treatment to be obtained, creating perspectives for redirecting gastric cancer therapy. Recently, proposed by The Cancer Genome Atlas Research Network (TCGA), GG was classified through the use of multiple and advanced molecular techniques in four subtypes called molecular subgroups: Epstein-Barr virus (EBV) positive; Unstable microsatellites (MSI); Stable genome (GS); and chromosomal instability (CIN). Each of these subtypes is characterized by its own genetic and epigenetic changes, which reflect on a specific phenotype. In addition, the molecular classification revealed new perspectives regarding the prognosis and treatment of GC. Thus, different molecular techniques and sequencing platforms have been used in the study of cancer genomics and translated to be applied in clinical practice. However, although the characterization of structural changes in genomes provides important information, it is important that these changes are evaluated in conjunction with other important aspects. Morphological characteristics, the contribution of the tumor microenvironment and the variation in protein expression - in addition to the patient's clinical evolution - should also be taken into account in order to have a better understanding of tumor heterogeneity and a complete view of the disease. Thus, the present study aims to evaluate genetic changes in patients with gastric adenocarcinoma according to the molecular subtypes of gastric cancer: EBV, MSI, GS and CIN. For the study, patients with gastric adenocarcinoma who underwent surgical between 2009 to 2016 at Instituto do Câncer do Estado de São Paulo (ICESP-HCFMUSP) will be retrospectively selected. The DNA extracted from the tumor samples will be subjected to second generation sequencing (Next Generation Sequencing - NGS) using the Illumina platform (MiSeq) for a panel of genes associated with solid tumors. The results obtained will be evaluated together with clinical, surgical, pathological, immunological and follow-up data - which we believe to understand the ideal scenario to better determine the impact of each change identified in the prognosis and survival. Thus, through the results obtained, we hope to contribute with information that will allow us to improve the treatment of GC and be closer to personalized medicine. (AU)

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