Banca de QUALIFICAÇÃO: MARÍLIA VIANA ALBUQUERQUE DE ALMEIDA

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
STUDENT : MARÍLIA VIANA ALBUQUERQUE DE ALMEIDA
DATE: 28/02/2020
TIME: 15:00
LOCAL: BioME - PPg-Bioinfo
TITLE:

Analysis and comparison of missense mutations in stomach adenocarcinoma and its structural consequences.

KEY WORDS:

stomach adenocarcinoma, missense mutations, residue interaction network

PAGES: 58
BIG AREA: Ciências Biológicas
AREA: Biologia Geral
SUMMARY:

In 2018, there were more than 18 million new cases of cancer in the world population and about 9.6 million deaths. In Brazil, during the 2020-2022 triennium, it is believed that 625 thousand new cases of cancer will occur; stomach cancer being the fifth most incident with a projection of 21 thousand new cases during the period. According to INCA data, in northeastern Brazil stomach cancer was among the top ten causes of death during the period from 2009 to 2013. it is among the main malignant neoplasms in the world, characterized by the disordered growth of cells, which invade tissues and organs. From the emergence of omic technologies, a deeper understanding of cancer-related genes and their respective mutations was obtained: deleterious (MD) - related to tumor progression; and neutral (MN) - unrelated to tumor progression. Approaches to computational tools and exploration of residue interaction networks (RINs) in proteins have been developed as a way to predict these types of mutations. Recent studies also suggest that some types of cancer may be related to environmental and hereditary factors; and others would be more strongly associated with stochastic factors such as random mutations that arise during DNA replication. The objective of the study is to analyze and compare missense mutations (MM) and their structural consequences related to stomach cancer (STAD), in addition to comparing them with cancer of different etiologies such as lung cancer (LUNG) and glioblastoma (GBM). Genes and their respective mutations were mined from The Cancer Genome Atlas (TCGA) and Catalog Of Somatic Mutations In Cancer (COSMIC) banks, and filtered by the Ndamage parameter (classification of the impact of the mutation). MMs that occurred in coding regions were selected. Three-dimensional protein structures (PDBs) were obtained from the pdb bank using UniProt codes. The positioning of the PDBs was mapped by the SIFTS information bank and the structural effect of the mutations was estimated from the construction of RINs, using the RING 2.0 software. Files containing Nodes (each amino acid in the protein) and Edges (connections between amino acids in the form of chemical interactions) were generated, such information added to the database and related to the mutations. The data were stored in MySQL. The Degree (connectivity between Nodes) was observed and this parameter was limited to 15. It was noted for the studied cancers that there is a high amount of mutations in Degrees with value up to five. As the Degree increases, the amount of MN decreases and the proportion of MD increases. In STAD and GBM, there is an increasing trend in MD as the Degree increases; in LUNG, MD remain constant and after increasing the Degree to 11, an increase in this type of mutation is noted. Regarding the exchange of 4 amino acids (AA), there is a greater proportion in STAD between AA of the polar type for aromatic and non-polar for positive charge; in GBM, from aromatic to positive charge and positive charge to positive charge, and in LUNG from aromatics to polar and non-polar to positive charge. The mutations are in low degrees, but MD tends to occur in nodes that are in higher degrees, as it is expected that greater connectivity can have a greater impact on proteins. Changes in chemical groups and their interactions may be associated with possible structural changes in proteins, having the potential to affect biological activity. From the assessment of its impacts on RIN, one can predict the effect of a mutation and associate it with the onset and progression of these types of cancer.

BANKING MEMBERS:
Presidente - 1513597 - JOAO PAULO MATOS SANTOS LIMA
Interno - 1267860 - GUSTAVO ANTONIO DE SOUZA
Interno - 2170415 - JORGE ESTEFANO SANTANA DE SOUZA