Genomic and epigenomic markers that helps in early diagnosis and monitoring of patients with colorectal cancer

• Grant number: 13/19268-3
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2014
• End date: July 31, 2016
• 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 (CRC) is a disease caused by genetic alterations. However, there is nowadays an increased interest in exploring on no genetic variations, as epigenetic factors. They could influence the etiology of complex diseases such as cancer, particularly in changes involving DNA methylation. Changes on gene expression due to DNA methylation contribute to events specific of cancer, causing the silence of tumor suppressor genes. Although the complete genetic basis for any complex human disease is not yet known, the re-sequencing of whole genomes and epigenomes is a promise to identify other causes of genetic variants involved in cancer disease. Aim: To analyze epigenetic changes (DNA methylation) of the whole human genome in CRC. To analyze the profile of genetic mutation of the genes KRAS , BRAF and PIK3CA to construct genetic and epigenetic gene panels to help on tumor classification. Patients: A case-control study will be done with CRC patients. The patients will be invited shortly after admission to the Hospital São Paulo, with surgical indication for resection of the tumor. The study will be done on 50 patients with CRC. On these patients the cancer and the normal mucosa adjacent to the tumor will be analized. Method : DNA will be extracted from the tissue using specific commercial kits . The DNA will be treated with bisulfite using the kit for DNA methylation (Cells -to- CpGTM Bisulfite Conversion Kit ® Reagents - Applied Biosystems). Methylation analysis will be performed using the technology Infinium Human Methylation 450 BeadChip ( Illumina Inc. ), The analysis of mutations in the genes KRAS , BRAF and PIK3CA will be performed with Kit developed by RANDOX®. (AU)

Scientific publications

(4)

(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)

MIRANDA, RAELSON RODRIGUES; SILVA, TIAGO DONIZETTI; FORONES, NORA MANOUKIAN. High-resolution melting for detecting KRAS mutations in colorectal cancer. BIOMEDICAL REPORTS, v. 11, n. 6, p. 269-273, DEC 2019. (13/19268-3)

RONALDO ELIEZER MAMELLI; ALEDSON VITOR FELIPE; TIAGO DONIZETTI SILVA; VANESSA HINZ; NORA MANOUKIAN FORONES. Expressão do RNAm e metilação do DNA do gene DKK2 em câncer colorretal. Arq. Gastroenterol., v. 58, n. 1, p. 55-60, 2021-04-23. (13/19268-3)

MIRANDA, RAELSON RODRIGUES; SILVA, TIAGO DONIZETTI; FORONES, NORA MANOUKIAN. High-resolution melting for detecting KRAS mutations in colorectal cancer. BIOMEDICAL REPORTS, v. 11, n. 6, p. 5-pg., 2019-12-01. (13/19268-3)

VICENTE CAVAGNARI, MARIANA ABE; SILVA, TIAGO DONIZETTI; HADDAD PEREIRA, MARCO ANTONIO; SAUER, LUISA JACQUES; SHIGUEOKA, DAVID; SAAD, SARHAN SYDNEY; BARAO, KATIA; DIAS RIBEIRO, CARLA CAROLINE; FORONES, NORA MANOUKIAN. Impact of genetic mutations and nutritional status on the survival of patients with colorectal cancer. BMC CANCER, v. 19, JUN 29 2019. (13/19268-3)