Identıfıcatıon of KRAS Mutatıons in Colorectal Carcınoma Patıents at Dr. M. Djamıl Hospıtal, West Sumatra-Indonesıa

Authors

  • Rita Maliza Biology Department, Faculty of Mathematics and Natural Sciences, Andalas University, Padang, West Sumatra, Indonesia
  • Hevi Horiza Sanitation, Health Polytechnic Tanjung pinang, Indonesia
  • Sumaryati Syukur Department of Chemistry, Faculty of Mathematics and Natural Science, Andalas University, Padang, West Sumatera, Indonesia
  • Allimuddin Tofrizal Faculty of Medicine, Department of Anatomical Pathology, Andalas University, Padang, West Sumatra, Indonesia
  • Bramadi Arya Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, Thailand

DOI:

https://doi.org/10.31964/mltj.v9i2.535

Keywords:

Colorectal cancer, kirsten rat sarcoma viral oncogene, mutation, polymerase chain reaction-sequencing

Abstract

Kirsten rat sarcoma viral oncogene (KRAS) gene mutations lead to abnormal activation of the RAS signalling pathway and have been associated with poor prognosis and resistance to some therapeutics. This study aimed to identify mutation characteristics of the KRAS genes codon 12 and 13 in colorectal cancer patients in West Sumatra. KRAS mutations were analyzed in 20 DNA of colorectal cancer patients' tissue samples by using polymerase chain reaction (PCR) with specific primer and direct sequencing analysis. Our findings showed five samples (25%) with mutated KRAS at codons 12 and 13 (including three samples with GGT→GAT, one sample with GGT→GTT in codon 12, and one sample with GGC→GAC in codon 13). In conclusion, we found two variations of amino acid changes at codon 12 (G12D and G12V) and one at codon 13 (G13D). More research with many samples is required to obtain conclusive data on the relationship between these gene mutations and colorectal cancer response to therapy and prognosis.

References

Abdullah, M., Wisaksono Sudoyo, A., Utomo, A. R., Fauzi, A., & Aziz Rani, A. (2012). Molecular profile of colorectal cancer in Indonesia: Is there another pathway? Gastroenterology and Hepatology From Bed to Bench, 5(2), 71–78.

Ahmad Kendong, S. M., Raja Ali, R. A., Nawawi, K. N. M., Ahmad, H. F., & Mokhtar, N. M. (2021). Gut Dysbiosis and Intestinal Barrier Dysfunction: Potential Explanation for Early-Onset Colorectal Cancer. Frontiers in Cellular and Infection Microbiology, 11, 744606. https://doi.org/10.3389/fcimb.2021.744606

Baskin, Y., Dagdeviren, Y. K., Calibasi, G., Canda, A. E., Sarioglu, S., Ellidokuz, H., & Oztop, I. (2014). KRAS mutation profile differences between rectosigmoid localized adenocarcinomas and colon adenocarcinomas. Journal of Gastrointestinal Oncology, 5(4), 265–269. https://doi.org/10.3978/j.issn.2078-6891.2014.038

Charitou, T., Srihari, S., Lynn, M. A., Jarboui, M. A., Fasterius, E., Moldovan, M., Shirasawa, S., Tsunoda, T., Ueffing, M., Xie, J., Xin, J., Wang, X., Proud, C. G., Boldt, K., Al-Khalili Szigyarto, C., Kolch, W., & Lynn, D. J. (2019). Transcriptional and metabolic rewiring of colorectal cancer cells expressing the oncogenic KRASG13D mutation. British Journal of Cancer, 121(1), 37–50. https://doi.org/10.1038/s41416-019-0477-7

Indrayani M, L. P. I., & Sriwidyani, N. P. (2017). K-RAS mutation profile in colorectal carcinoma patients in Sanglah Hospital Denpasar, Bali-Indonesia. Bali Medical Journal, 3(3), 40–42. https://doi.org/10.15562/bmj.v3i3.717

Irfan, H. P. (2019). Karakteristik Pasien Kanker Kolorektal di RSUP DR. M. Djamil Padang Periode Januari – Desember 2017 (Diploma Thesis). Universitas Andalas.

Jones, R. P., Sutton, P. A., Evans, J. P., Clifford, R., McAvoy, A., Lewis, J., Rousseau, A., Mountford, R., McWhirter, D., & Malik, H. Z. (2017). Specific mutations in KRAS codon 12 are associated with worse overall survival in patients with advanced and recurrent colorectal cancer. British Journal of Cancer, 116(7), 923–929. https://doi.org/10.1038/bjc.2017.37

Levi, M., Prayogi, G., Sastranagara, F., Sudianto, E., Widjajahakim, G., Gani, W., Mahanadi, A., Agnes, J., Khairunisa, B. H., & Utomo, A. R. (2017). Clinicopathological Associations of K-RAS and N-RAS Mutations in Indonesian Colorectal Cancer Cohort. Journal of Gastrointestinal Cancer, 49(2), 124–131. https://doi.org/10.1007/s12029-016-9901-x

Levin-Sparenberg, E., Bylsma, L. C., Lowe, K., Sangare, L., Fryzek, J. P., & Alexander, D. D. (2020). A Systematic Literature Review and Meta-Analysis Describing the Prevalence of KRAS, NRAS, and BRAF Gene Mutations in Metastatic Colorectal Cancer. Gastroenterology Research, 13(5), 184–198. https://doi.org/10.14740/gr1167

Li, W., Liu, Y., Cai, S., Yang, C., Lin, Z., Zhou, L., Liu, L., Cheng, X., & Zeng, W. (2019). Not all mutations of KRAS predict poor prognosis in patients with colorectal cancer. Int J Clin Exp Patho, 12(3), 957–967.

Mastutik, G., Rahniayu, A., Rahaju, A. S., Kurniasari, N., & I’tishom, R. (2016). The mutatıon status of KRAS gene codon 12 and 13 ın colorectal adenocarcınoma. Indonesian Journal of Clinical Pathology and Medical Laboratory, 23(1), 12–17. http://www.indonesianjournalofclinicalpathology.or.id

Meng, M., Zhong, K., Jiang, T., Liu, Z., Kwan, H. Y., & Su, T. (2021). The current understanding of the impact of KRAS on colorectal cancer. Biomedicine and Pharmacotherapy, 140. https://doi.org/10.1016/j.biopha.2021.111717

Miyakura, Y., Sugano, K., Fukayama, N., Konishi, F., & Nagai, H. (2002). Concurrent Mutations of K-ras Oncogene at Codons 12 and 22 in Colon Cancer. In Jpn J Clin Oncol, 32(6):219-21. doi: 10.1093/jjco/hyf043

Ni Nyoman, A. D., Suksmarini, N. M. P. W., Pranata, A. A. N. S., Rompis, A. Y., & Sumadi, I. W. J. (2022). The prevalence of KRAS and BRAF mutation in colorectal cancer patients in Bali. Indonesian Journal of Biotechnology, 27(1), 29–35. https://doi.org/10.22146/ijbiotech.67506

Nistal, E., Fernández-Fernández, N., Vivas, S., & Olcoz, J. L. (2015). Factors determining colorectal cancer: The role of the intestinal microbiota. Frontiers in Oncology, 5, 220. https://doi.org/10.3389/fonc.2015.00220

Pangribowo, S. (2019). Info Datin Beban Kanker di Indoensia. Kementerian Kesehatan RI Pusat Data dan Informasi. Accessed 14 March 2022, https://www.studocu.com/id/document/universitas-udayana/antropologi-kesehatan/infodatin-kanker-2019/32696320

Rachmawati, M., Yulianti, H., Hernowo, B. S., Suryanti, S., Wijaya, I., Rahadiani, N., Heriyanto, D. S., & Irianiwati, I. (2019). The Correlation of KRASGene Expression and P53 Immunoexpression in Colorectal Adenocarcinoma. Open Access Macedonian Journal of Medical Sciences, 7(12), 1940–1945. https://doi.org/10.3889/oamjms.2019.548

Roa, I., Sanchez, T., Majlis, A., & Schalper, K. (2013). KRAS gene mutation in colorectal cancer. Rev Med Chil, 141, 1166–1172.

Saleh, I., Triwani, Hayati, L., Surya Fatimah, L., & Subandrate. (2019). Identification of KRAS gene codon 12 polymorphism in colorectal cancer patients at Mohammad Hoesin General Hospital Palembang. Journal of Physics: Conference Series, 1246(1). https://doi.org/10.1088/1742-6596/1246/1/012051

Molenaar, R. J., Radivoyevitch, T., & Wilmink, J. W. (2017). RE: Colorectal Cancer Incidence Patterns in the United States, 1974–2013. Journal of the National Cancer Institute, 109(8). https://doi.org/10.1093/jnci/djw322

Tsunoda, T., Takashima, Y., Fujimoto, T., Koyanagi, M., Yoshida, Y., Doi, K., Tanaka, Y., Kuroki, M., Sasazuki, T., & Shirasawa, S. (2010). Three-dimensionally specific inhibition of DNA repair-related genes by activated KRAS in colon crypt model. Neoplasia, 12(5), 397–404. https://doi.org/10.1593/neo.10170

Van Cutsem, E., Köhne, C. H., Láng, I., Folprecht, G., Nowacki, M. P., Cascinu, S., Shchepotin, I., Maurel, J., Cunningham, D., Tejpar, S., Schlichting, M., Zubel, A., Celik, I., Rougier, P., & Ciardiello, F. (2011). Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: Updated analysis of overall survival according to tumour KRAS and BRAF mutation status. Journal of Clinical Oncology, 29(15), 2011–2019. https://doi.org/10.1200/JCO.2010.33.5091

Zahari, A., & Sudiyatmo. (2011). Hereditary non-polyposis colorectal cancer (lynch syndrome) pada wanita umur 16 tahun. Majalah Kedokteran Andalas, 35(2), 172-180

Downloads

Published

2023-12-23

How to Cite

Maliza, R., Horiza, H., Syukur, S., Tofrizal, A., & Arya, B. (2023). Identıfıcatıon of KRAS Mutatıons in Colorectal Carcınoma Patıents at Dr. M. Djamıl Hospıtal, West Sumatra-Indonesıa. Medical Laboratory Technology Journal, 9(2). https://doi.org/10.31964/mltj.v9i2.535

Issue

Section

Articles