Article type: Research Article
Authors: Bagci, Binnura; b; * | Sari, Musac | Karadayi, Kursatd | Turan, Mustafad | Ozdemir, Ozturke | Bagci, Gokhanf
Affiliations: [a] Department of Nutrition and Dietetics, Faculty of Health Sciences, Cumhuriyet University, Sivas, Turkey | [b] Advanced Technology Research Center (CÜTAM), Cumhuriyet University, Sivas, Turkey | [c] Department of Biology, Faculty of Science, Cumhuriyet University, Sivas, Turkey | [d] Department of General Surgery, Faculty of Medicine, Cumhuriyet University, Sivas, Turkey | [e] Department of Medical Genetics, Faculty of Medicine, On Sekiz Mart University, Çanakkale, Turkey | [f] Department of Medical Genetics, Faculty of Medicine, Cumhuriyet University, Sivas, Turkey
Correspondence:
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Corresponding author: Binnur Bagci, Department of Nutrition and Dietetics, Faculty of Health Sciences, Cumhuriyet University, 58140 Sivas, Turkey. Tel.: +90 346 2192523; Fax: +90 346 2191261; E-mail:binnur.koksal@hotmail.com
Abstract: BACKGROUND: Colorectal cancer is a serious disease that causes
significant morbidity and mortality in developed countries. Genetic changes,
such as mutations in proto-oncogenes and DNA repair genes, and loss of
function in the tumor suppressor genes cause colorectal cancer development.
Abnormal DNA methylation is also known to play a crucial role in colorectal
carcinogenesis. OBJECTIVE: In this study, frequencies of KRAS and BRAF mutations,
promoter hypermethylation profiles of SFRP2, DAPK1, MGMT, HIC1 and p16
genes, and possible associations between hypermethylation of these genes and
KRAS and BRAF mutations were aimed to find out. METHODS: Ninety three colorectal cancer tissues and 14 normal colon
mucosas were included in the study. Common twelve KRAS gene mutation were
investigated with using reverse-hybridization strip assay method. BRAF V600E
mutations were investigated with RFLP method. Hypermethylation status of
five tumor suppressor genes were detected by using reverse-hybridization
strip assay method after bisulfite modification of DNA. RESULTS: KRAS and BRAF mutation frequencies were determined as
54.84% and 12.9%, respectively. Promoter hypermethylation frequencies
of tumor suppressor genes SFRP2, DAPK1, MGMT, HIC1 and p16 were determined
as 66.7%, 45.2%, 40.9%, 40.9% and 15.1%, respectively.
Statistically significant associations were found between BRAF mutation and
SFRP2 and p16 tumor suppressor genes hypermethylation (SFRP2; p= 0.005, p16;
p= 0.016). Compared to rectum, SFRP2 (p= 0.017) and MGMT (p= 0.013) genes have
statistically significantly higher promoter hypermethylation in colon. CONCLUSIONS: Results of the current study have confirmed that KRAS
mutations and SFRP2 hypermethylation can be used as genetic markers in
colorectal cancer.
Keywords: Colorectal cancer, hypermethylation, oncogene, tumor suppressor gene, KRAS, BRAF, SFRP2, DAPK1, MGMT, HIC1, p16
DOI: 10.3233/CBM-160624
Journal: Cancer Biomarkers, vol. 17, no. 2, pp. 133-143, 2016
