Investigation of mutational signatures in gastric adenocarcinomas and evaluation of its possible prognostic impacts

Abstract

Gastric Adenocarcinomas (GAs) are highly aggressive neoplasms with a high incidence in Brazil. The highest world rates of GA's mortality are due to few clinical signs of the disease in its early stages, which leads to late detection in most cases. Because of strong genetic and environmental component in GA etiology, the search for the causing somatic mutations processes that contribute to its formation and progression, may help in the understanding of tumor biology in an evolutionary context and, thus, allow advances in prognosis and in the establishment of therapeutic approaches. Due to the lack of studies that associate molecular characteristics to the clinic, as well as the lack of large scale molecular studies in Brazilian population, this study aims to analyze the mutational profile of GAs samples from this population, looking for molecular signatures that may be associated with relevant clinical aspects. The employed genomic data will be generated within the objectives of a thematic project recently approved by FAPESP (14 / 26897-0) and contrasted with global data produced by TCGA. To detect mutational signature of tumor samples a computer and statistical method developed by the Laboratory of Bioinformatics and Computational Biology from CIPE will be employed. At the end, we intend to contribute to a better understanding of the mechanisms involved in tumorigenesis in different GAs subtypes, with potential impact in the clinical practice.