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Molecular Profile of Colorectal Cancer Patients in Bali Based on Methylation of O^6-Methylguanine DNA Methyltransferase Promoter Region and Mutation of BRAF and Kirsten RAt Sarcoma Viral Oncogene Homolog Gene
摘要
Background: Analysis of O^6-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 ＜10%, unmethylated). Direct sequencing showed no mutation (V600E) of BRAF gene and 11 (22.5%) samples with mutated KRAS which was 9 (18.4%) and 2 (4.1%) samples mutated at codons 12 and 13, respectively. Immunohistochemistry results showed that from 29 methylated MGMT, 19 (65.5%) samples had low expression and 10 (34.5%) samples had high expression of MGMT. Conclusions: Altogether, our result showed that most of the samples showed MGMT methylation and it tended to decrease the expression of MGMT. In addition, BRAF and KRAS mutations were exclusively occurred. These data give a contribution to the situation of MGMT methylation and BRAF and KRAS mutations in CRC patients in Denpasar whose data are limited. Further studies are needed to identify the key molecular pathway of CRC that will be potential for CRC management.
延伸閱讀
- Liang, J. T., Huang, K. C., Lai, H. S., & Lee, P. H. (2006). Primary Mutation of Exon 3 of β-catenin (CTNNB1) Gene in Colorectal Tumors: Correlation with Mutation of Adenomatous Polyposis Coli Gene, Microsatellite Instability, and Prognostic Significance. Formosan Journal of Surgery, 39(6), 279-292. https://doi.org/10.29833/FJS.200612.0001
- 李建佑（2010）。Promoter Methylation Status of Tumor Suppressor Genes and an Inflammatory-related COX-2 Gene in Cervical Intraepithelial Neoplasia〔碩士論文，高雄醫學大學〕。華藝線上圖書館。https://doi.org/10.6832/KMU.2010.00148
- Sasaki, S., Watanabe, T., & Nakayama, H. (2013). Analysis of the mRNA Expression of Chemotherapy-Related Genes in Colorectal Carcinoma Using the Danenberg Tumor Profile Method. Journal of Oncology, 2013(), 186-192. https://doi.org/10.1155/2013/386906
- 林育麟（2014）。The biological significance and clinical implication of KRAS mutant-mediated oxaliplatin chemotherapy sensitivity in metastatic colorectal cancer (mCRC)〔博士論文，國立臺灣大學〕。華藝線上圖書館。https://doi.org/10.6342/NTU.2014.01770
- Lin, H. C., Cheng, C. C., Huang, C. S., Huang, J. H., & Ho, A. S. (2022). Evaluation of Carcinoembryonic Antigen, Vascular Endothelial Growth Factor, Neutrophil Elastase as Serological Biomarkers in Patients with Colorectal Cancer. 中華民國大腸直腸外科醫學會雜誌, 33(2), 51-59. https://doi.org/10.6312/SCRSTW.202206_33(2).11026