Evaluation of informativeness of DNA methylation degree of DKK4 gene as a diagnostic criterion in breast adenocarcinoma.
DOI:
https://doi.org/10.26641/2307-0404.2014.3.28509Keywords:
DNA methylation, DKK4 gene, CG site, breast adenocarcinomaAbstract
Abnormalities of DNA methylation play a significant role in initiation and progression of tumors. The aim of the study was the evaluation of the quantitative determination of hypermethylation of DKK4 gene first exon as a biomarker of the breast epithelial cells malignant transformation in patients with adenocarcinoma (2-3 stage). The analysis of DNA methylation was performed by quantitative pyrosequencing using the set PSQ96MA (Qiagen, USA). It was established that DKK4 methylated DNA content in breast adenocarcinoma tissue samples significantly exceeds the same indexes in the unchanged breast tissue taken from the same patients. The average methylated DNA level in conditions of breast cancer equals to 36,8±12,63 percents whereas the same normal breast indexes equal to 19,37±7,1 percents, р≤0,01. The increased content of methylated DNA in DKK4 gene first exon was revealed in 20 samples of breast adenocarcinoma tissues out of 23 (86.96%, P ≤ 0,01); in the rest 3 samples the investigated content of methylated DNA was comparable with the same index in the normal breast tissues.References
Correction of PCR-bias in quantitative DNA met¬hylation studies by means of cubic polynomial reg¬ression / E.A. Moskalev, M.G. Zavgorodnij, S.P. Majorova [et al.] // Nucleic Acids Res. — 2011. — Vol. 39.— e77.
Dapper 1 antagonizes Wnt signaling by promo¬ting dishevelled degradation / L. Zhang, X. Gao, J. Wen, Y. Ning [et al.] // J. Biol. Chem. - 2006. - Vol. 281. - P. 8607-8612.
Deletions of chromosome 8p and loss of SFRP1 expression are progression markers of papillary bladder cancer / R. Stoehr, C. Wissmann, H. Suzuki [et al.] // Lab. Invest. — 2004. — Vol. 84. — P. 465–478.
DNA hypermethylation accompanied by trans¬criptional repression in follicular lymphoma / L.B. Ben¬nett, J.L. Schnabel, J.M. Kelchen [et al.] // Genes Chro¬mo¬somes Cancer. — 2009.— Vol. 48.— P. 828–841.
Epigenetic inactivation of the Wnt antagonist DICKKOPF-1 (DKK-1) gene in human colorectal cancer / O. Aguilera, M.F. Fraga, E.Ballestar [et al.] // Oncogene. — 2006. — Vol. 25. — P. 4116–4121.
Epigenetic inactivation of SFRP genes allows con¬stitutive WNT signaling in colorectal cancer / H. Su¬zuki, D.N. Watkins, K.W. Jair [et al.] / Nat. Genet. — 2004. — Vol. 36. — P. 417–422.
Frequent epigenetic inactivation of SFRP genes and constitutive activation of Wnt signaling in gastric can¬cer / M. Nojima, H. Suzuki, M. Toyota [et al.] // Oncogene. — 2007. — Vol. 26 . — P. 4699–4713.
Frequent epigenetic inactivation of Wnt anta¬gonist genes in breast cancer / H. Suzuki, M. Toyota, H. Ca¬raway [et al.] // Br. J. Cancer. — 2008. — Vol. 98. — P. 1147–1156.
HDPR1, a novel inhibitor of the WNT/beta-cate¬nin signaling, is frequently downregulated in hepatocel¬lular carcinoma: involvement of methylation-mediated gene silencing / T.O. Yau, C.Y. Chan, K.L. Chan, [et al.] // Oncogene. — 2005. — Vol. 24. — P. 1607–1614.
Loss of SFRP1 is associated with breast cancer progression and poor prognosis in early stage tumors / E. Klopocki, G. Kristiansen, P.J. Wild [et al.] // Int. J. Oncol. — 2004. — Vol. 25. — P. 641–649.
Niehrs C. Function and biological roles of the Dick¬kopf family of Wnt modulators / C. Niehrs // Oncogene. — 2006. — Vol. 25. — P. 7469–7481.
Polakis P. Wnt signaling and cancer / P. Polakis // Genes Dev. — 2000. — Vol. 14. — P. 1837–1851.
Kawano Y. Secreted antagonists of the Wnt sig¬naling pathway / Y. Kawano, R. Kypta // J. Cell Sci. — 2003. — Vol. 116. — P. 2627–2634.
Small molecule inhibitors of Wnt/beta-cate¬nin/lef-1 signaling induces apoptosis in chronic lympho¬cytic leukemia cells in vitro and in vivo / R.K. Gan¬dhirajan, P.A. Staib, K. Minke [et al.] // Neoplasia. — 2010. — N 12. — P. 326–335.
Moskalev EA, Zavgorodnij MG, Majorova SP, Vorobjev IA, Jandaghi P, Bure IV, Hoheisel JD. Cor¬rection of PCR-bias in quantitative DNA methylation stu¬dies by means of cubic polynomial regression. Nucleic Acids Res. 2011;39:e77.
Zhang L, Gao X, Wen J, Ning Y, Chen YG. Dap¬per 1 antagonizes Wnt signaling by promoting dishevelled degradation. J Biol Chem. 2006;281:8607–12.
Stoehr R, Wissmann C, Suzuki H. et al.Deletions of chromosome 8p and loss of SFRP1 expression are pro¬gression markers of papillary bladder cancer. Lab. Invest. 2004;84:465–78.
Bennett LB, Schnabel JL, Kelchen JM, Taylor KH, Guo J, Arthur GL, Papageorgio CN, Shi H, Caldwell CW. DNA hypermethylation accompanied by transcrip¬tional repression in follicular lymphoma. Genes Chromo¬somes Cancer. 2009;48:828–41.
Aguilera O, Fraga MF, Ballestar E, Paz MF, Her¬ranz M, Espada J, García JM, Muñoz A, Esteller M, Gon¬zález-Sancho JM. Epigenetic inactivation of the Wnt antagonist DICKKOPF-1 (DKK-1) gene in human colo¬rectal cancer. Oncogene. 2006;25:4116–21.
Suzuki H, Watkins DN, Jair KW. et al. Epigenetic inactivation of SFRP genes allows constitutive WNT sig¬naling in colorectal cancer. Nat. Genet. 2004;36:417–22.
Nojima M, Suzuki H, Toyota M. et al. Frequent epigenetic inactivation of SFRP genes and constitutive activation of Wnt signaling in gastric cancer. Oncogene. 2007;26:4699–713.
Suzuki H, Toyota M, Caraway H. et al. Frequent epigenetic inactivation of Wnt antagonist genes in breast cancer. Br. J. Cancer. 2008;98:1147–56.
Yau TO, Chan CY, Chan KL, Lee MF, Wong CM, Fan ST, Ng IO. HDPR1, a novel inhibitor of the WNT/beta-catenin signaling, is frequently downregulated in hepatocellular carcinoma: involvement of methylation-mediated gene silencing. Oncogene. 2005;24:1607–14.
Klopocki E, Kristiansen G, Wild PJ. et al. Loss of SFRP1 is associated with breast cancer progression and poor prognosis in early stage tumors. Int. J. Oncol. 2004;25:641–9.
Niehrs C. Function and biological roles of the Dick¬kopf family of Wnt modulators. Oncogene. 2006;25:7469–81.
Polakis P. Wnt signaling and cancer. Genes Dev. 2000;14:1837–51.
Kawano Y, Kypta R. Secreted antagonists of the Wnt signaling pathway. J. Cell Sci. 2003;116:2627–34.
Gandhirajan RK, Staib PA, Minke K, Gehrke I, Plickert G, Schlösser A, Schmitt EK, Hallek M, Kreuzer KA. Small molecule inhibitors of Wnt/beta-catenin/lef-1 signaling induces apoptosis in chronic lymphocytic leu¬ke¬mia cells in vitro and in vivo. Neoplasia. 2010;12:326–35.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2017 Medical Perspectives
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Submitting manuscript to the journal "Medicni perspektivi" the author(s) agree with transferring copyright from the author(s) to publisher (including photos, figures, tables, etc.) editor, reproducing materials of the manuscript in the journal, Internet, translation into other languages, export and import of the issue with the author’s article, spreading without limitation of their period of validity both on the territory of Ukraine and other countries. This and other mutual duties of the author and all co-authors separately and editorial board are secured by written agreement by special form to use the article, the sample of which is presented on the site.
Author signs a written agreement and sends it to Editorial Board simultaneously with submission of the manuscript.
