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ORIGINAL ARTICLE

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


1 Department of Biochemistry, Faculty of Medicine, Udayana University, Denpasar, Indonesia
2 Department of Pathology, Faculty of Medicine, Udayana University, Denpasar, Indonesia
3 Institute of Molecular Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan

Correspondence Address:
Ayu Dewi Ni Nyoman,
Jl. PB. Sudirman, Denpasar 80232
Indonesia
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jmedsci.jmedsci_205_19

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 <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.


 

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