Novel Alterations of Some Mitochondrial tRNA Genes in Vienamese Colorectal Cancer Patients
Authors: Bich Pham Thi , Van Nguyen Thi , To Ta Van , Thai Trinh Hong 
Published: March 2019

Some mutations of mt-DNA which encode tRNA (mt-tRNA) were previously reported  to be associated with clinical manifestations of neuromuscular disorders syndrome. In addition, alterations of the mitochondrial genome have been suggested to contribute to mitochondrial dysfunction and tumorigenesis. Alterations in some mt-tRNA genes have also been identified in breast cancer, lung cancer and colorectal cancer. However, so far, we have not found any report on mt-tRNA gene alteration in the Vietnamese colorectal cancer patients. So that, in this study, we analyzed the alterations of some mt-tRNA genes in a group of  Vietnamese colorectal cancer patients and predicted influence of the alterations to secondary structure of tRNA based on bioinformatic tools. PCR-RFLP and DNA sequencing methods were used to screening alterations, secondary structure of tRNA was predicted in silico by using a tool of the  Vienna RNA Websuite. Results: both A12309G and A12310G of tRNALeu were identified together in two out of 98 patients, and both T12150G and C12154G of tRNAHis were indentified in one  out of 19 patients. All of these alterations were heteroplasmic and have not been reported in cancer patients. In particular, the C12154G  alteration in the DHR loop led to change of secondary structure of  tRNAHis and may affect to function of this tRNA molecule.

Keywords

mt-tRNA, Vietnamese colorectal cancer, PCR-RFLP, DNA sequencing

References

[1] http://globocan.iarc.fr/Pages/online.aspx (30/11/2017).[2] M. Brandon, P. Baldi, D.C Wallace, Mitochodrial mutations in cancer, Oncogen 25(34) (2006) 4647.[3] G. Li, YX. Duan, XB. Zhang, F Wu, Mitochondrial RNA mutations may be infrequent in hepatocellular carcinoma patients, Genet Mol Res15(2) (2016) doi: 10.4238/gmr.15027665.[4] F. Mohammed, AR. Rezaee, E. Mosaieby, M. Houshmand, Mitochondrial A12308G alteration in RNA Leu (CUN)) in colorectal cancer samples, Diagn Pathol (2015) doi: 10.1186/s13000-015-0337-6.[5] S. Datta, M. Majumder, NK. Biswas, N. Sikdar, B. Roy, Increased risk of oral cancer in relation to common Indian mitochondrial polymorphisms and Autosomal GSTP1 locus, Cancer, 110 (2007) 1999.[6] L .Wang , ZJ. Chen , YK. Zhang , HB. Le, The role of mitochondrial RNA mutations in lung cancer, Int J Clin Exp Med 8(8) (2015) 13341.[7] AR. Gruber, R. Lorenz, SH. Bernhart, R. Neubock, IL Hofacker The Vienna ARN Websuite, Nucleic Acids Res 36 (2008) 70.[8] https://blast.ncbi.nlm.nih.gov/Blast.cgi (11/2017).[9] Y. Goto, I Nonaka, S Horai, A mutation in the RNALeu (UUR) gene associated with the MELAS subgroup of mitochondrial encephalomyopathies, Nature 348(6302 (1990) 651[10] http://www.mitomap.org/MITOMAP (11/2017).[11] A. Lorenc, J. Bryk Golik P, Homoplasmic MELAS A3243G mtDNA mutation in a colon cancer sample, Mitochondrion 3(2) (2003) 119.[12] EL. Blakely, J.W Yarham , C.L. Alston , K Craig , J. Poulton , C. Brierley , SM. Park , A. Dean , JH. Xuereb , KN. Anderson , A. Compston , C. Allen , S. Sharif , P. Enevoldson , M. Wilson , SR. Hammans , DM. Turnbull , R. McFarland , RW.Taylor , Pathogenic mitochondrial tRNA point mutations: nine novel mutations affirm their importance as a cause of mitochondrial disease, Hum Mutat 34(9) (2013) 1260.[13] S. DiMauro, Mitochondrial ADN medicine, Biosci Rep 27(3) (2007) 5.[14] DC. Wallace, D. Chalkia, Mitochondrial ADN genetics and the heteroplasmy conundrum in evolution and disease”, Cold Spring Harb Perspect Biol 5(11) (2013), doi:10.1101/cshperspect. a021220