Molecular study of BRAF gene polymorphisms and the association with mtDNA copy number in thyroid cancer

Main Article Content

Hawraa Abdul-Hameed
Zainab Nizar Jawad
Heba Abdul-Salam
Haidar Hamza Al-Abidy

Keywords

Polymorphism , mtDNA , BRAF , ND1 , TC , SNP

Abstract

TC is one of the most common types of endocrine cancer in the world, the incidence of thyroid cancer has increased recently, ranking 13th among the most common cancers and the most sixth among women. Females had the highest incidence of illness and death compared to males. Thyroid cancer has been associated with genetic changes where mtDNA and its relationship to the Cancer have been studied, the morphological variations in the BRAF gene and their effect on TC patients have been studied.. The study samples were collected from patients of Warith International Cancer Institute in Kerbala / Iraq, the study included (100 samples) were 50 for patients and 50 for control , DNA measured inside mitochondria by Quantitive Polymerase Chain Reaction (QPCR) , and morphological variations of the BRAF gene were detected on 5 samples of patients against one of control sample with the sequencing the result of this study was shown that there is two new SNPs (rs2128998142 and rs2128998351) were detected in the BRAF gene and the current study found an association with thyroid cancer. The mtDNA content was associated with the risk of thyroid cancer, copy number of mitochondrial DNA for the ND1 gene compared to the normal HGB gene increased by a very large percentage in patients with thyroid cancer for the control group. Our findings lead us to hypothesize that an increase in the number of mitochondrial DNA copies in leukocytes may be associated with oxidative DNA damage and operate as a separate risk factor for thyroid cancer ( TC )

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References

1. Al-Ankoshy, A. A. M., Alqershi, K. A., & Rabeea, H. W. (2020). The Role of BRAF Mutation (V600E) in Papillary Thyroid Carcinoma (PTC). Indian Journal of Forensic Medicine & Toxicology, 14(1), 1369-1373.
2. Anari, S., Tataei Sarshar, N., Mahjoori, N., Dorosti, S., & Rezaie, A. (2022). Review of deep learning approaches for thyroid cancer diagnosis. Mathematical Problems in Engineering, 2022.
3. Esfahanian, F., Hazaveh, M. M., Garehbagh, L. H., Falahati, K., Ataei, M., Sanati, M. H., & Jadali, Z. (2021). Increased Mitochondrial DNA Copy Number and Oxidative Damage in Patients with Hashimoto’s Thyroiditis. Iranian Journal of
Public Health, 50(8), 1697.
4. Han Y, Chen JZ. Oxidative stress induces mitochondrial DNA damage and cytotoxicity through independent mechanisms in human cancer cells. Biomed Res Int. (2013) 2013:825065. doi 10.1155/2013/825065
5. He J, Wei WQ, Zhang SW, Zheng RS, Ma F, Wang N, et al. 2018 China Cancer Registry Annual Report. Beijing: People's Medical Publishing House (2019).
6. He, W. J., Li, C., Huang, Z., Geng, S., Rao, V. S., Kelly, T. N., ... & Rebholz, C. M. (2022). Association of mitochondrial DNA copy number with risk of progression of kidney disease. Clinical Journal of the American Society of Nephrology, 17(7), 966-975.
7. Hussain, A. M., & Lafta, R. K. (2021). Cancer trends in Iraq 2000–2016. Oman medical journal, 36(1), e219.
8. Kaubryte J and Lai AG: Pan-cancer prognostic genetic mutations and clinicopathological factors associated with survival outcomes: a systematic review. NPJ Precis Oncol 6(1): 27, 2022. PMID: 35444210. DOI: 10.1038/s41698-022-00269-5 .
9. Kitahara, C. M., & Schneider, A. B. (2022). Epidemiology of Thyroid Cancer. Cancer Epidemiology, Biomarkers & Prevention, 31(7), 1284-1297.
10. Kyrodimos, E., Chrysovergis, A., Mastronikolis, N., Papanastasiou, G., Tsiambas, E., Spyropoulou, D., ... & Papanikolaou, V. (2023). The Landscape of Single Nucleotide Polymorphisms in Papillary Thyroid Carcinoma. Landscape, 3(1).
11. Lam, A. K. (2022). Papillary thyroid carcinoma: current position in epidemiology, genomics, and classification. In Papillary Thyroid Carcinoma: Methods and Protocols (pp. 1-15). New York, NY: Springer US.
12. Lee MH, Lee SE, Kim DW, Ryu MJ, Kim SJ, Kim SJ, et al. Mitochondrial localization and regulation of BRAFV600E in thyroid cancer: a clinically used RAF inhibitor is unable to block the mitochondrial activities of BRAFV600E. J Clin Endocrinol Metab. (2011) 96:E19–30. doi: 10.1210/jc.2010-1071.
13. Lence-Anta JJ, Xhaard C, Ortiz RM, Kassim H, Pereda CM, Turcios S, Velasco M, Chappe M, Infante I, Bustillo M, García A, Clero E, Maillard S, Salazar S, Rodriguez R and de Vathaire F: Environmental, lifestyle, and anthropometric risk factors for differentiated thyroid cancer in cuba: a case-control study. Eur Thyroid J 3(3): 189-196, 2014. PMID: 25538901. DOI: 10.1159/000362928.
14. Lim LM, Chung WY, Hwang DY, Yu CC, Ke HL, Liang PI, Lin TW, Cheng SM, Huang AM and Kuo HT: Whole-exome sequencing identified mutational profiles of urothelial carcinoma post kidney transplantation. J Transl Med 20(1): 324, 2022. PMID: 35864526. DOI: 10.1186/s12967-022-03522-4.
15. Perdas, E.; Stawski, R.; Kaczka, K.; Nowak, D.; Zubrzycka, M. Altered Levels of Circulating Nuclear and Mitochondrial DNA in Patients with Papillary Thyroid Cancer. Sci. Rep. 2019, 9, 14438.
16. Shaalan, A. A., Mokhtar, S. H., Ahmedah, H. T., Almars, A. I., Toraih, E. A., Ibrahiem, A. T., ... & Salem, M. A. (2022). Prognostic Value of LINC-ROR (rs1942347) Variant in Patients with Colon Cancer Harboring BRAF Mutation: A Propensity Score-Matched Analysis. Biomolecules, 12(4),569.
17. Shimizu, Y., Maruyama, K., Suzuki, M., Kawachi, H., Low, S. K., Oh-Hara, T., ... & Katayama, R. (2022). Acquired resistance to BRAF inhibitors is mediated by BRAF splicing variants in BRAF V600E mutation-positive colorectal neuroendocrine carcinoma. Cancer Letters, 543, 215799.
18. Stratton MR, Campbell PJ and Futreal PA: The cancer genome. Nature 458(7239): 719-724, 2009. PMID: 19360079. DOI: 10.1038/nature07943.
19. Thakur, N., Sharma, A. K., Singh, H., & Singh, S. (2020). Role of mitochondrial DNA (mtDNA) variations in cancer development: A systematic review. Cancer Investigation, 38(7), 375-393.
20. Tuchalska-Czuroń, J., Lenart, J., Augustyniak, J., & Durlik, M. (2019). Is mitochondrial DNA copy number a good prognostic marker in resectable pancreatic cancer?. Pancreatology, 19(1), 73-79.
21. Weeks, K. S., Kahl, A. R., Lynch, C. F., & Charlton, M. E. (2018). Racial/ethnic differences in thyroid cancer incidence in the United States, 2007‐2014. Cancer, 124(7), 1483-1491.
22. Zainab,N,J,and Awad, W.(2020). Association of urokinase and Vitamin D receptor genes SNPs and urolithiasis in an Iraqi population, Meta Gene, 2020, 24, 100679
23. Zainab,N,J.(2023). Association Between APC Gene SNPs and the Risk of Occurrence of Colorectal Cancer. AIP Conference Proceedingsthis, 2414, 020021.
24. Zheng, J., Cui, N. H., Zhang, S., Wang, X. B., & Ming, L. (2019). Leukocyte mitochondrial DNA copy number and risk of thyroid cancer: A two-stage case-control study. Frontiers in Endocrinology, 10, 421.