Study of microsatellite instability and potential target genes in GISTs

• Grant number: 12/01732-2
• Support Opportunities: Scholarships in Brazil - Master
• Start date: July 01, 2012
• End date: March 31, 2014
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Rui Manuel Vieira Reis
• Grantee: Nathália Cristina Campanella
• Host Institution: Hospital do Câncer de Barretos. Fundação Pio XII (FP). Barretos , SP, Brazil

Abstract

The GISTs are the most common mesenchymal tumors of the gastrointestinal tract. Most of these tumors harbour mutations that activate the oncogenes KIT and PDGFRA, encoding a tyrosine kinase receptors, thus inducing a constitutive activation of their functions and consequent tumor development. However, other mechanisms are crucial to the pathogenesis of GIST, it becomes crucial to elucidate these paths towards an understanding and proper treatment of these tumors. The microsatellite instability (MSI), is a type of genetic instability, which has been found in several tumor types such as colorectal, endometrial, among others, and which plays a central role in carcinogenesis. MSI occurs in repeating regions of genomic DNA (microsatellite) due to inactivation of genes responsible for DNA repair mechanism. This can occur in DNA coding regions which mutation are responsible for tumor development. In the presence of MSI in GISTs is virtually unknown. In this sense, our project aims to assess the presence and frequency of MSI from a population of 140 GISTs. In the cases with MSI, we'll study the expression of the DNA repair proteins (MSH2, MLH1, PMS2 and MSH-6) by immunohistochemistry, study of the MLH1 gene methylation and assess the presence of mutations in key genes. Finally we will correlate the presence of MSI and molecular changes with clinical-pathological data of GISTs. With this work we want to contribute to identifying new avenues that carcinogenic can contribute to the development of new therapeutic and prognostic tools in GISTs.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

CAMPANELLA, NATHALIA C.; BERARDINELLI, GUSTAVO N.; SCAPULATEMPO-NETO, CRISTOVAM; VIANA, DANILO; PALMERO, EDENIR I.; PEREIRA, RUI; REIS, RUI M.. Optimization of a pentaplex panel for MSI analysis without control DNA in a Brazilian population: correlation with ancestry markers. European Journal of Human Genetics, v. 22, n. 7, p. 875-880, JUL 2014. (12/01732-2)

CAMPANELLA, NATHALIA C.; DE OLIVEIRA, ANTONIO T.; SCAPULATEMPO-NETO, CRISTOVAM; GUIMARAES, DENISE P.; REIS, RUI M.. Biomarkers and Novel Therapeutic Targets in Gastrointestinal Stromal Tumors (GISTs). Recent Patents on Anti-Cancer Drug Discovery, v. 8, n. 3, p. 288-297, SEP 2013. (12/01732-2)