HRM screening of the UBC9 gene encoding the SUMO-E2-conjugating enzyme — case-control study in breast cancer
DOI:
https://doi.org/10.32471/exp-oncology.2312-8852.vol-42-no-2.14739Keywords:
breast cancer, gene polymorphism, high resolution melting method, sumoylation, UBC9 geneAbstract
Summary. Aim: UBC9 (E2) small ubiquitin-like modifier conjugating enzyme plays a key role in the post-translational modification of proteins named sumoylation. Defects in small ubiquitin-like modifier modification may contribute to breast carcinogenesis. In the present work, we examined UBC9 genetic variation. Materials and Methods: UBC9 genetic variation was analyzed by using the high resolution melting (HRM) method. HRM study was conducted on 173–182 healthy women and 188–190 women with breast cancer. Results: During HRM screening, we analysed three known single-nucleotide polymorphisms in introns: rs4984806, rs909916 and rs909917, and one known single nucleotide polymorphism rs8063 in exon 7, in a non-coding region. The genotype frequencies for all polymorphisms were in accordance with Hardy — Weinberg equilibrium among the control subjects and breast cancer patients. The linkage disequilibrium analysis displayed that there was one polymorphism block, which consisted of three single nucleotide polymorphisms: rs909916, rs909917 and rs4984806. We identified two common haplotypes CCG and TTC, but we did not find significant differences in the distribution of these haplotypes between cases and controls. Conclusion: Our study showed no differences in the occurrence of indicated polymorphisms in the UBC9 gene in a group of healthy women compared to women with breast cancer. These results suggest that the polymorphisms of the UBC9 gene — rs4984806, rs909916, rs909917 and rs8063 can be not associated with breast cancer risk.
References
Bettermann K, Benesch M, Weis S, et al. SUMOylation in carcinogenesis. Cancer Lett 2012; 316: 113–25.
Alshareeda AT, Negm OH, Green AR, et al. SUMOylation proteins in breast cancer. Breast Cancer Res Treat 2014; 144: 519–30.
Hay RT. Decoding the SUMO signal. Biochem Soc Transact 2013; 41: 463–73.
Synowiec E, Krupa, R, Morawiec Z, et al. Efficacy of DNA double-strand breaks repair in breast cancer is decreased in carriers of the variant allele of the UBC9 gene c.73G>A polymorphism. Mutat Res 2010; 694: 31–8.
Wozniak K, Krupa R, Synowiec E, et al. Polymorphism of UBC9 gene encoding the SUMO-E2-conjugating enzyme and breast cancer risk. Pathol Oncol Res 2014; 20: 67–72.
Strapagiel D, Sobalska-Kwapis M, Slomka M, et al. Biobank Lodz — DNA based biobank at the University of Lodz, Poland. Open J. Bioresources 2016; 3: p.e6.
Koszarska M, Kucsma N, Kiss K, et al. Screening the expression of ABCB6 in erythrocytes reveals an unexpectedly high frequency of Lan mutations in healthy individuals. PLoS One 2014; 9: e111590.
Słomka M, Sobalska-Kwapis M, Korycka-Machała M, et al. Genetic variation of the ABC transporter gene ABCC1 (Multidrug resistance protein 1 — MRP1) in the Polish population. BMC Genetics 2015; 16: 114.
Mueller JC. Linkage disequilibrium for different scales and applications. Brief Bioinform 2004; 5: 355–64.
Shifman S, Kuypers J, Kokoris M, et al. Linkage disequilibrium patterns of the human genome across populations. Hum Mol Genetics 2003; 12: 771–6.
Karamouzis MV, Konstantinopoulos PA, Badra FA, et al. SUMO and estrogen receptors in breast cancer. Breast Cancer Res Treat 2008; 107: 195–210.
Abdel-Hafiz HA, Horwitz KB. Control of progesterone receptor transcriptional synergy by SUMOylation and deSUMOylation. BMC Mol Biol 2012; 1: 10.
Galanty Y, Belotserkovskaya R, Coates J, et al. Mammalian SUMO E3-ligases PIAS1 and PIAS4 promote responses to DNA double-strand breaks. Nature 2009; 7275: 935–9.
Morris JR, Boutell C, Keppler M, et al. The SUMO modification pathway is involved in the BRCA1 response to genotoxic stress. Nature 2009; 7275: 886–90.
Xu J, Watkins T, Reddy A, et al. A novel mechanism whereby BRCA1/1a/1b fine tunes the dynamic complex interplay between SUMO-dependent/independent activities of Ubc9 on E2-induced ERalpha activation/repression and degradation in breast cancer cells. Int J Oncol 2009; 34: 939–49.
McGuire A, Brown JAL, Malone C, et al. Effects of age on the detection and management of breast cancer. Cancers 2015; 7: 908–29.
Didkowska J, Wojciechowska U. Cancer in Poland in 2013. Krajowy Rejestr Nowotworów. 2015; ISSN 0867-8251, Warszawa.
Dünnebier T, Bermejo JL, Haas S, et al. Common variants in the UBC9 gene encoding the SUMO-conjugating enzyme are associated with breast tumor grade. Int J Cancer 2009; 125: 596−602.
Dünnebier T, Bermejo JL, Haas S, et al. Polymorphisms in the UBC9 and PIAS3 genes of the SUMO-conjugating system and breast cancer risk. Breast Cancer Res Treat 2010; 121: 185–94.
Gabriel SB, Schaffner SF, Nguyen H, et al. The structure of haplotype blocks in the human genome. Science 2002; 296: 2225–9.
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