Molecular Profile of Colorectal Cancer Patients in Bali Based on Methylation of O6-Methylguanine DNA Methyltransferase Promoter Region and Mutation of BRAF and Kirsten RAt Sarcoma Viral Oncogene Homolog Gene

Abstract

Background: Analysis of O6-methylguanine DNA methyltransferase (MGMT) methylation considers as a predictive marker for chemotherapy sensitivity. Mutation in BRAF and Kirsten RAt sarcoma viral oncogene homolog (KRAS) gene is also crucial in colorectal tumorigenesis which is associated with primary resistance to epidermal growth factor receptor therapy. This study was aimed to identify the methylation of MGMT gene and to detect BRAF and KRAS mutations in colorectal cancer (CRC). Methods: The methylation level of MGMT gene was measured by pyrosequencing from bisulfite-treated DNA. Direct sequencing was performed to identify BRAF and KRAS mutations. The expression of MGMT was evaluated by immunohistochemistry. Results: Analysis of MGMT methylation showed that 15 (30%) samples were classified as Group 1 (mean range ≥27%, methylated), 27 (54%) samples were Group 2 (mean range: 10%–26%, intermediate), and 8 (16%) samples were Group 3 (mean range