Genetic changes in fecal and tissue DNA in colorectal cancer patients

• Grant number: 09/16618-8
• Support Opportunities: Regular Research Grants
• Start date: January 01, 2010
• End date: December 31, 2012
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Nora Manoukian Forones
• Grantee: Nora Manoukian Forones
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Colorectal cancer is the third cause of cancer in the world, including Brazil. The estimated risk for the Brazilian population is 13 cases for 100,000 for men and 15cases for 100,000 persons for women. In colorectal cancer carcinogenesis, many genetic alterations occur in the DNA. The lost of the function of the protein APC, after the mutation of the tumor suppressor gene, stimulates the cellular proliferation is the first change in colorectal cancer carcinogenesis. In K-ras and BRAF genes the mutations may permanently activate the transcription of the proteins and cause the transformation of the normal colonic epithelium to adenoma. The mutation of p53 (the guardian of the genome) and consequent inactivation of the protein can be the cause of the alteration in the cellular cycle and apoptosis. These alterations may be found also in the stools. The aim of this study is to detect these genes mutation in the stools and compare with the presence of these alterations the tumor.150 subjects with colonoscopy indication will be studied and sub-divided in 3 groups according to the findings of the exam: normal, presence of polyps or cancer. TP53, K-ras, APC and BRAF DNA mutations will be analyzed in the feces and the tissues of these patients by the methodology RANPLEXCRC (Randox Clinical Diagnostic Solutions), based on the simultaneous detection of the 28 mutations of these genes by microarray. The proceedings for the identification had as the beginning the enrichment of the DNA with primers containing the mutations by MPCR reaction (Multiplex Polymerase Chain Reactions).The first MPCR amplificates simultaneously the K-ras, BRAF and TP53 genes and the second the APC gene. After that it will be done the hybridization, ligation and amplification of the probes for microarray analysis (Biochip Array Technology).The intention of this study is to describe the sensibility and specificity of a non invasive method to diagnose colorectal cancer and polyps. (AU)

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)

YOLANDA TEIXEIRA; JACQUELINE MIRANDA LIMA; MARIA LUIZA ALMEIDA PRADO OLIVEIRA SOUZA; PEDRO AGUIAR JR; TIAGO DONIZETTI SILVA; NORA MANOUKIAN FORONES. HUMAN DNA QUANTIFICATION IN THE STOOLS OF PATIENTS WITH COLORECTAL CANCER. Arq. Gastroenterol., v. 52, n. 4, p. 293-298, 2015-12-00. (09/16618-8)