The presence of A5935G, G5949A, G6081A, G6267A, T9540C mutations in MT-CO1 and MT-CO3 genes and other variants of MT-CO1 and MT-CO3 gene fragments in the study population diagnosed with endometrial cancer
Abstract
Objectives: The specific purpose of this study was the assessment of A5935G, G5949A, G6081A, G6267A mutations in MT-CO1 and T9540C in MT-CO3, and alterations detected during the analysis of MT-CO gene fragments in subject and control groups. A secondary aim was to assess the relationship between MT-CO1 and MT-CO3 gene alterations and endometrial cancer incidence and evaluation of the prognostic value of MT-CO1 and MT-CO3 gene alterations.
Material and methods: In this study, we investigated A5935G, G5949A, G6081A, G6267A mutations in MT-CO1 and T9540C in MT-CO3, and alterations detected during the analysis of MT-CO gene fragments in formalin-fixed, paraffin-embedded endometrial and benign endometrial hyperplasia of a cohort of 125 subjects.
Results: The T9540C mutation in MT-CO3 was detected in one patient from the subject group. None of the remaining mutations were detected. The research showed that the presence of alterations in MT-CO1 and MT-CO3 typical of other types of cancer is not a risk factor for endometrial cancer. Analysis of MT-CO1 and MT-CO3 gene fragments revealed 10 alterations (6 and 4 respectively). The alterations detected were identified in 10% of the tested group and 8% of the control group.
Conclusions: The research showed that the presence of alterations in MT-CO1 (A5935G, G5949A, G6081A, G6267A) typical of other types of cancer is not a risk factor for endometrial cancer. Three new alterations detected in this study (A6052G, A9545G, G9575A) were described for the first time.
Keywords: mtDNA mutationsalterations in MT-CO1alterations in MT-CO3endometrial cancer
References
- Petros JA, Baumann AK, Ruiz-Pesini E, et al. mtDNA mutations increase tumorigenicity in prostate cancer. Proc Natl Acad Sci U S A. 2005; 102(3): 719–724.
- Gallardo ME, Moreno-Loshuertos R, López C, et al. m.6267G>A: a recurrent mutation in the human mitochondrial DNA that reduces cytochrome c oxidase activity and is associated with tumors. Hum Mutat. 2006; 27(6): 575–582.
- Czarnecka AM, Golik P, Bartnik E. Mitochondrial DNA mutations in human neoplasia. J Appl Genet. 2006; 47(1): 67–78.
- Brandon M, Baldi P, Wallace DC. Mitochondrial mutations in cancer. Oncogene. 2006; 25(34): 4647–4662.
- Czarnecka A, Bartnik E. Mitochondrial DNA mutations in tumors. Cellular Respiration and Carcinogenesis. 2008: 119–130.
- Papa S, Capitanio N, Capitanio G, et al. Protonmotive cooperativity in cytochrome c oxidase. Biochim Biophys Acta. 2004; 1658(1-2): 95–105.
- Plak K, Kukwa W, Bartnik E, et al. Występowanie mutacji w mtDNA i ich potencjalny wpływ na strukturę białek w wybranych typach nowotworów. Postępy Biochemii. 2008; 54: 151–160.
- D'Aurelio M, Pallotti F, Barrientos A, et al. In vivo regulation of oxidative phosphorylation in cells harboring a stop-codon mutation in mitochondrial DNA-encoded cytochrome c oxidase subunit I. J Biol Chem. 2001; 276(50): 46925–46932.
- Betts MJ, Russell BR. Amino acid properties and consequences of substitutions. In: Barnes MR. ed. Bioinformatics for Geneticists. Second edition. John Wiley & Sons, Ltd 2007: 311–342.
- Tsukihara T, Aoyama H, Yamashita E, et al. The whole structure of the 13-subunit oxidized cytochrome c oxidase at 2.8 A. Science. 1996; 272(5265): 1136–1144.
- Liu VWS, Yang HJ, Wang Y, et al. High frequency of mitochondrial genome instability in human endometrial carcinomas. Br J Cancer. 2003; 89(4): 697–701.
- Ferenc T, Olszewska-Słonina D, Bratkowska W. Ekspresja genów. In: Drewa G, Ferenc T. ed. Podstawy genetyki dla studentów i lekarzy. Wydanie II poprawione i uzupełnione. Wydawnictwo Medyczne Urban & Partner, Wrocław 2003: 55–90.
- Kirches E, Krause G, Warich-Kirches M, et al. High frequency of mitochondrial DNA mutations in glioblastoma multiforme identified by direct sequence comparison to blood samples. Int J Cancer. 2001; 93(4): 534–538.
- Jones JB, Song JJ, Hempen PM, et al. Detection of mitochondrial DNA mutations in pancreatic cancer offers a "mass"-ive advantage over detection of nuclear DNA mutations. Cancer Res. 2001; 61(4): 1299–1304.
- Challen C, Brown H, Cai C, et al. Mitochondrial DNA mutations in head and neck cancer are infrequent and lack prognostic utility. Br J Cancer. 2011; 104(8): 1319–1324.
- Chiu PM, Liu VWS, Ngan HYS, et al. Detection of mitochondrial DNA mutations in gestational trophoblastic disease. Hum Mutat. 2003; 22(2): 177.
- Máximo V, Soares P, Lima J, et al. Mitochondrial DNA somatic mutations (point mutations and large deletions) and mitochondrial DNA variants in human thyroid pathology: a study with emphasis on Hürthle cell tumors. Am J Pathol. 2002; 160(5): 1857–1865.
- Earp MA, Brooks-Wilson A, Cook L, et al. Inherited common variants in mitochondrial DNA and invasive serous epithelial ovarian cancer risk. BMC Res Notes. 2013; 6: 425.
- Data were designed from Uni Prot database [online], http://www.uniprot.org/ [access: 1.02.2015].
- Tan DJ, Bai RK, Wong LJC. Comprehensive scanning of somatic mitochondrial DNA mutations in breast cancer. Cancer Res. 2002; 62(4): 972–976.
- Wani AA, Sharma N, Shouche YS, et al. Nuclear-mitochondrial genomic profiling reveals a pattern of evolution in epithelial ovarian tumor stem cells. Oncogene. 2006; 25(47): 6336–6344.
- Nishikawa M, Oshitani N, Matsumoto T, et al. Accumulation of mitochondrial DNA mutation with colorectal carcinogenesis in ulcerative colitis. Br J Cancer. 2005; 93(3): 331–337.
- Beckman KB, Ames BN. Detection and quantification of oxidative adducts of mitochondrial DNA. Methods Enzymol. 1996; 264: 442–453.
- Beckman KB, Ames BN. Oxidative decay of DNA. J Biol Chem. 1997; 272(32): 19633–19636.
- Khrapko K, Coller HA, André PC, et al. Mitochondrial mutational spectra in human cells and tissues. Proc Natl Acad Sci U S A. 1997; 94(25): 13798–13803.
- Cadet J, Berger M, Douki T, et al. Oxidative damage to DNA: formation, measurement, and biological significance. Rev Physiol Biochem Pharmacol. 1997; 131: 1–87.
