Abstract
Aberrant methylation of regulation regions of tumorsuppressor genes is showed for many cancer diseases. In course of this modification an enzyme DNMT3 methylates RCGY sites in CpG-islands of regulation regions producing R(5mC)GY sites. Earlier we developed GLAD-PCR assay to determine R(5mC)GY site in a definite position of human genome. In this work we have applied GLAD-PCR assay to determine R(5mC)GY sites in regulation regions of ESR1 and ELMO1 tumor-suppressor genes. We have studied a fragment of first exon of ELMO1 gene and a part of ESR1 promoter region in DNA preparations from malignant cell line SW837 and colorectal tumor samples. We have checked four sites in each region and found two highly methylated sites: GCGC in first exon of ELMO1 gene and GCGT in promoter region of ESR1 gene. Site GCGT is weakly methylated in healthy tissues and more methylated in the most of colorectal samples. Site GCGC is not methylated in healthy tissues and significantly methylated in 60% of colorectal samples. A possibility to use GLAD-PCR assay for cancer diagnostics is discussed.References
Абдурашитов М.А., Чернухин В.А., Томилов В.Н. и др. Рестрикционный анализ ДНК человека - новые возможности в ДНК-диагностике // Мед. генетика. 2007.- Т. 6. - № 8. - С. 29-36.
Киселева Н.П., Лихтенштейн А.В. В кн.: Канцерогенез / Под ред. Д.Г. Заридзе. М., - 2004.
Кузнецов В.В., Акишев А.Г., Абдурашитов М.А., Дегтярев С.Х. Способ определения нуклеотидной последовательности Pu(5mC)Py в заданном положении протяженной ДНК // Патент РФ № 2525710. - 2013.
Смит К., Клко С., Кантор Ч. Анализ генома. Методы / Под ред. К. Дейвиса. М., - 1990.
Caiazza F., Ryan E.J., Doherty G. et al. Estrogen receptors and their implications in colorectal carcinogenesis // Front. Oncol. - 2015. - Vol. 5. - P. 19.
de Caseres I.I., Cairus P. Methylated DNA sequences for early cancer detection, molecular classification and chemotherapy response prediction // Clin. Transl. Oncol. - 2007. - Vol. 9. - N 7. - P 429-437.
Handa V., Jeltsch A. Profound sequence preference of Dnmt3a and Dnmt3b mammalian DNA methyl-transferases shape the human epigenome // J. Mol. Biol. - 2005. - Vol. 348. - N 5. - P 1103-1112.
Kibriya M.G., Raza M., Jasmine F. et al. A genome-wide DNA methylation study in colorectal carcinoma // BMC Med. Genomics. - 2011. - Vol. 4. - P. 50.
LaPointe L.C., Pedersen S.K., Dunne R. et al. Discovery and validation of molecular biomarkers for colorectal adenomas and cancer with application to blood testing // PLoS One. - 2012. - Vol. 7:e29059.
Lao V.V., Grady W.M. Epigenetics and colorectal cancer // Nat. Rev. Gastroenterol. Hepatol. - 2011. - Vol. 8. - P 686-700.
Mishra D.K., Chen Z., Wu Y et al. Global methylation pattern of genes in androgen-sensitive and androgen-independent prostate cancer cells // Mol. Cancer Ther. - 2010. - Vol. 9. - N 1. - P. 33-45.
Mitchell S.M., Ross J.P, Drew H.R. et al. A panel of genes methylated with high frequency in colorectal cancer // BMC Cancer. - 2014. - Vol. 14. - P. 54.
Tarasova G. V., Nayakshina T.N., Degtyarev S. Kh. Substrate specificity of new methyl-directed DNA endonuclease GlaI // BMC Mol. Biol. - 2008. - Vol. 9:7.
Umer M., Herceg Z. Deciphering the epigenetic code: an overview of DNA methylation analysis methods // Antioxid. Redox. Signal. - 2013. - Vol. 18. - P. 1972-1986.
Yagi K., Akagi K., Hayashi H. et al. Three DNA methylation epigenotypes in human colorectal cancer // Clin. Cancer Res. - 2010. - Vol. 16. - N 1. - P. 21-33.
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