Biopolym. Cell. 2010; 26(6):450-460.
Genetic and epigenetic changes in malignant cells of tumors of urogenital organs
1Gordiyuk V. V.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680


More than 90 % of human malignant neoplasms are presented by epithelial tumors. Cancer of urogenital organs is a serious problem because of wide spread of disease and high mortality rates. Tumorogenesis is associated with different defects of genetic apparatus of cells as well as epigenetic factors (DNA methylation disorders, chromatin reorganizations in processes of histones modifications, regulation of gene expression with small non-coding RNAs). In this review we analyzed genetic and epigenetic changes in the urogenital tumors.
Keywords: cancer of urogenital organs, modifications of histones, DNA methylation, oncogenes, mutations


[1] Miller S., Lavker R. M., Sun T. T. Interpreting epithelial cancer biology in the context of stem cells: Tumor properties and therapeutic implications Biochim. Biophys. Acta 2005 1756, N 1:25–35.
[2] Lazarevich N. L., Fleishman D. I. Tissue-specific transcription factors in progression of epithelial tumors Biochemistry 2008 73, N 5:573–591.
[3] AJCC Cancer Staging Handbook New-York: Springer, 2002 423 p.
[4] Cancer in Ukraine, 2004–2005. Ukrainian cancer registry statistics, 2006 Bull. of national cancer registry of Ukraine (engl.). Ed. C. O. Shalimov Kyiv, 2006.
[5] Negm R. S., Verma M., Srivastava S. The promise of biomarkers in cancer screening and detection Trends Mol. Med 2002 8, N 6:288–293.
[6] Huh Y. O., Lin K. I., Vega F., Schlette E., Yin C. C., Keating M. J., Luthra R., Medeiros L. J., Abruzzo L. V. MYC translocation in chronic lymphocytic leukaemia is associated with increased prolymphocytes and a poor prognosis Br. J. Haematol 2008 142, N 1:36–44.
[7] Chang I. W., Huang H. Y., Sung M. T. Melanotic Xp11 translocation renal cancer: a case with PSF-TFE3 gene fusion and up-regulation of melanogenetic transcripts Amer. J. Surg. Pathol 2009 33, N 12:1894–1901.
[8] Clark J. P., Cooper C. S. ETS gene fusions in prostate cancer Nat. Rev. Urol 2009 6, N 8:429–439.
[9] Wang G., Vasquez K. M. Z-DNA, an active element in the genome Front. Biosci 2007 12:4424–4438.
[10] Stark G. R. Regulation and mechanisms of mammalian gene amplification Adv. Cancer Res 1993 61:87–113.
[11] Kamath A., Tara H., Xiang B., Bajaj R., He W., Li P. Doubleminute MYC amplification and deletion of MTAP, CDKN2A, CDKN2B, and ELAVL2 in an acute myeloid leukemia characterized by oligonucleotide-array comparative genomic hybridization Cancer Genet. Cytogenet 2008 183, N 2:117–120.
[12] Hansel D. E., Swain E., Dreicer R., Tubbs R. R. HER2 overexpression and amplification in urothelial carcinoma of the bladder is associated with MYC coamplification in a subset of cases Amer. J. Clin. Pathol 2008 130, N 2:274–281.
[13] Nakayama K., Nakayama N., Jinawath N., Salani R., Kurman R. J., Shih Ie. M., Wang T. L. Amplicon profiles in ovarian serous carcinomas Int. J. Cancer 2007 120, N 12:2613–2617.
[14] Lassus H., Sihto H., Leminen A., Joensuu H., Isola J., Nupponen N. N., Butzow R. Gene amplification, mutation, and protein expression of EGFR and mutations of ERBB2 in serous ovarian carcinoma J. Mol. Med 2006 84, N 8:671– 681.
[15] Kuo M. T. Roles of multidrug resistance genes in breast cancer chemoresistance Adv. Exp. Med. Biol 2007 608:23–30.
[16] Olaharski A. J., Sotelo R., Solorza-Luna G., Gonsebatt M. E., Guzman P., Mohar A., Eastmond D. A. Tetraploidy and chromosomal instability are early events during cervical carcinogenesis Carcinogenesis 2006 27, N 2:337–343.
[17] Capo-chichi C. D., Cai K. Q., Testa J. R., Godwin A. K., Xu X. X. Loss of GATA6 leads to nuclear deformation and aneuploidy in ovarian cancer Mol. Cell Biol 2009 29, N 17:4766–4777.
[18] Yasuhara T., Okamoto A., Kitagawa T., Nikaido T., Yoshimura T., Yanaihara N., Takakura S., Tanaka T., Ochiai K., Ohtake Y. FGF7-like gene is associated with pericentric inversion of chromosome 9, and FGF7 is involved in the development of ovarian cancer. Int. J. Oncol. 2005; 26(5):1209–1216.
[19] Li A. J., Karlan B. Y. Genetic factors in ovarian carcinoma Curr. Oncol. Rep 2001 3, N 1:27–32.
[20] Yap K. P., Ang P., Lim I. H., Ho G. H., Lee A. S. Detection of a novel Alu-mediated BRCA1 exon 13 duplication in Chinese breast cancer patients and implications for genetic testing Clin. Genet 2006 70, N 1:80–82.
[21] Montagna M., Santacatterina M., Torri A., Menin C., Zullato D., Chieco-Bianchi L., D'Andrea E. Identification of a 3 kb Alu-mediated BRCA1 gene rearrangement in two breast/ ovarian cancer families Oncogene 1999 15, N 28– P. 4160–4165.
[22] Plesec T. P., Hunt J. L. KRAS mutation testing in colorectal cancer Adv. Anat. Pathol 2009 16, N 4:196–203.
[23] Greenblatt M. S., Bennett W. P., Hollstein M., Harris C. C. Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis. Cancer Res. 1994; 54(18):4855–4878.
[24] Hughes D. J. Use of association studies to define genetic modifiers of breast cancer risk in BRCA1 and BRCA2 mutation carriers Fam. Cancer 2008 7, N 3:33–44.
[25] Vermeulen L., Sprick M. R., Kemper K., Stassi G., Medema J. P. Cancer stem cells – old concepts, new insights Cell Death. Differ 2008 68, N 4:1213–1220.
[26] Loeb L. A., Bielas J. H., Beckman R. A. Cancers exhibit a mutator phenotype: clinical implications Cancer Res 2008 68, N 10:3551–3557.
[27] Groen R. W., Oud M. E., Schilder-Tol E. J., Overdijk M. B., ten Berge D., Nusse R., Spaargaren M., Pals S. T. Illegitimate WNT pathway activation by beta-catenin mutation or autocrine stimulation in T-cell malignancies Cancer Res 2008 68, N 17:6969–6977.
[28] Liu H., Mulholland N., Fu H., Zhao K. Cooperative activity of BRG1 and Z-DNA formation in chromatin remodeling Mol. Cell Biol 2006 26, N 7:2550–2559.
[29] Jenuwein T., Allis C. D. Translating the histone code Science 2001 293, N 5532:1074–1080.
[30] Ma Y., Fan S., Hu C., Meng Q., Fuqua S. A., Pestell R. G., Tomita Y. A., Rosen E. M. BRCA1 regulates acetylation and ubiquitination of estrogen receptor-{alpha} Mol. Endocrinol 2010 24, N 1:76–90.
[31] Gibbons R. J. Histone modifying and chromatin remodeling enzymes in cancer and dysplastic syndromes Hum. Mol. Genet 2005 14, N 1:85–92.
[32] Varambally S., Cao Q., Mani R.-Sh., Shankar S., Wang X., Ateeq B., Laxman B., Cao X., Jing X., Ramnarayanan K., Brenner J. Ch., Yu J., Kim J. H., Han B., Tan P., KumarSinha Ch., Lonigro R. J., Palanisamy N., Maher Ch., Chinnaiyan A. M. Genomic loss of microRNA-101 leads to overexpression of histone methyltransferase EZH2 in cancer Science 2008 322, N 5908:1695–1699.
[33] Simon J. A, Lange C. A. Roles of the EZH2 histone methyltransferase in cancer epigenetics Mutat. Res 2008 647, N 1–2:21–29.
[34] Fritzsche F. R., Weichert W., Ruske A., Gekeler V., Beckers T., Stephan C., Jung K., Scholman K., Denkert C., Dietel M., Kristiansen G. Class I histone deacetylases 1, 2 and 3 are highly expressed in renal cell cancer BMC Cancer 2008 8:381.
[35] Lin Z., Bazzaro M., Wang M. C., Chan K. C., Peng S., Roden R. B. Combination of proteasome and HDAC inhibitors for uterine cervical cancer treatment Clin. Cancer Res 2009 15, N 2:570–577.
[36] Weichert W., Denkert C., Noske A., Darb-Esfahani S., Dietel M., Kalloger S. E., Huntsman D. G., Kobel M. Expression of class I histone deacetylases indicates poor prognosis in endometrioid subtypes of ovarian and endometrial carcinomas. Neoplasia. 2008; 10(9):1021–1027.
[37] Wei Y., Xia W., Zhang Z., Liu J., Wang H., Adsay N. V., Albarracin C., Yu D., Abbruzzese J. L., Mills G. B., Bast R. C. Jr., Hortobagyi G. N., Hung M. C. Loss of trimethylation at lysine 27 of histone H3 is a predictor of poor outcome in breast, ovarian, and pancreatic cancers Mol. Carcinogen 2008 47, N 9:701–706.
[38] Iizuka M., Takahashi Y., Mizzen C. A., Cook R. G., Fujita M., Allis C. D., Frierson H. F. Jr., Fukusato T., Smith M. M. Histone acetyltransferase Hbo1: catalytic activity, cellular abundance, and links to primary cancers Gene 2009 436, N 1– 2:108–114.
[39] Cha T. L., Chuang M. J., Wu S. T., Sun G. H., Chang S. Y., Yu D. S., Huang S. M., Huan S. K., Cheng T. C., Chen T. T., Fan P. L., Hsiao P. W. Dual degradation of aurora A and B kinases by the histone deacetylase inhibitor LBH589 induces G2-M arrest and apoptosis of renal cancer cells Clin. Cancer Res 2009 15, N 3:840–850.
[40] Krieg A. J., Rankin E. B., Chan D., Razorenova O., Fernandez S., Giaccia A. J. Regulation of the histone demethylase JMJD1A by HIF-1{alpha} enhances hypoxic gene expression and tumor growth Mol. Cell Biol 2010 30, N 1:344– 353.
[41] Seligson D. B., Horvath S., McBrian M. A., Mah V., Yu H., Tze S., Wang Q., Chia D., Goodglick L., Kurdistani S. K. Global levels of histone modifications predict prognosis in different cancers Am. J. Pathol 2009 174, N 5:1619– 1628.
[42] Xiong S. D., Yu K., Liu X. H., Yin L. H., Kirschenbaum A., Yao S., Narla G., Difeo A., Wu J. B., Yuan Y., Ho S. M., Lam Y. W., Levine A. C. Ribosome-inactivating proteins isolated from dietary bitter melon induce apoptosis and inhibit histone deacetylase-1 selectively in premalignant and malignant prostate cancer cells Int. J. Cancer 2009 125, N 4:774– 782.
[43] Ke X. S., Qu Y., Rostad K., Li W. C., Lin B., Halvorsen O. J., Haukaas S. A., Jonassen I., Petersen K., Goldfinger N., Rotter V., Akslen L. A., Oyan A. M., Kalland K. H. Genome-wide profiling of histone h3 lysine 4 and lysine 27 trimethylation reveals an epigenetic signature in prostate carcinogenesis PLoS One 2009 4, N 3:e4687.
[44] Zeng Y., Abdallah A., Lu J. P., Wang T., Chen Y. H., Terrian D. M., Kim K., Lu Q. delta-Catenin promotes prostate cancer cell growth and progression by altering cell cycle and survival gene profiles Mol. Cancer 2009 10, N 8:19.
[45] Porkka K. P., Pfeiffer M. J., Waltering K. K., Vessella R. L., Tammela T. L. J., Visakorpi T. MicroRNA expression profiling in prostate cancer Cancer Res 2007 67, N 13– P. 6130– 6135.
[46] Yu J., Ryan D. G., Getsios S., Oliveira-Fernandes M., Fatima A., Lavker R. M. MicroRNA-184 antagonizes microRNA-205 to maintain SHIP2 levels in epithelia Proc. Nat. Acad. Sci. USA 2008 105, N 49:19300–19305.
[47] Lee D. Y., Deng Z., Wang C. H., Yang B. B. MicroRNA-378 promotes cell survival, tumor growth, and angiogenesis by targeting SuFu and Fus-1 expression Proc. Nat. Acad. Sci. USA 2007 104, N 51:20350–20355.
[48] Lodygin D., Tarasov V., Epanchintsev A., Berking C., Knyazeva T., Korner H., Knyazev P., Diebold J., Hermeking H. Inactivation of miR-34a by aberrant CpG methylation in multiple types of cancer Cell Cycle 2008 7, N 16–P. 2591– 2600.
[49] Noonan E. J., Place R. F., Pookot D., Basak S., Whitson J. M., Hirata H., Giardina C., Dahiya R. miR-449a targets HDAC-1 and induces growth arrest in prostate cancer Oncogene 2009 28, N 14:1714–1724.
[50] Jung M., Mollenkopf H. J., Grimm C., Wagner I., Albrecht M., Waller T., Pilarsky C., Johannsen M., Stephan C., Lehrach H., Nietfeld W., Rudel T., Jung K., Kristiansen G. MicroRNA profiling of clear cell renal cell cancer identifies a robust signature to define renal malignancy J. Cell Mol. Med 2009 13(9B):3918-28
[51] Toloubeydokhti T., Bukulmez O., Chegini N. Potential regulatory functions of microRNAs in the ovary Semin. Reprod. Med 2008 26, N 6:469–478.
[52] Yang N., Kaur S., Volinia S., Greshock J., Lassus H., Hasegawa K., Liang S., Leminen A., Deng S., Smith L., Johnstone C. N., Chen X. M., Liu C. G., Huang Q., Katsaros D., Calin G. A., Weber B. L., Butzow R., Croce C. M., Coukos G., Zhang L. MicroRNA microarray identifies Let-7i as a novel biomarker and therapeutic target in human epithelial ovarian cancer Cancer Res 2008 68, N 24:10307– 10314.
[53] Iorio M. V., Visone R., Di Leva G., Donati V., Petrocca F., Casalini P., Taccioli C., Volinia S., Liu C. G., Alder H., Calin G. A., Munard S., Croce C. M. MicroRNA signatures in human ovarian cancer Cancer Res 2007 67, N 18:8699–8707.
[54] Huang Y. W., Liu J. C., Deatherage D. E., Luo J., Mutch D. G., Goodfellow P. J., Miller D. S., Huang T. H. Epigenetic repression of microRNA-129-2 leads to overexpression of SOX4 oncogene in endometrial cancer Cancer Res 2009 69, N 23:9038–9046.
[55] Wang X., Wang H. K., McCoy J. P., Banerjee N. S., Rader J. S., Broker T. R., Meyers C., Chow L. T., Zheng Z. M. Oncogenic HPV infection interrupts the expression of tumor-suppressive miR-34a through viral oncoprotein E6 RNA 2009 15, N 4:637–647.
[56] Datta J., Kutay H., Nasser M. W., Nuovo G. J., Wang B., Majumder S., Liu C. G., Volinia S., Croce C. M., Schmittgen T. D., Ghoshal K., Jacob S. T. Methylation mediated silencing of MicroRNA-1 gene and its role in hepatocellular carcinogenesis Cancer Res 2008 68, N 13:5049–5058.
[57] Calin G. A., Croce C. M. MicroRNA signatures in human cancers Nat. Rev. Cancer 2006 6, N 11:857–866.
[58] Strathdee G., Davies B. R., Vass J. K., Siddiqui N., Brown R. Cell type-specific methylation of an intronic CpG island controls expression of the MCJ gene Carcinogenesis 2004 25, N 5:693–670.
[59] Venter J. C., Adams M. D., Myers E. W., Li P. W., et al. The sequence of the human genome Science 2001 291, N 5507:1304–1351.
[60] Bird A. The essentials of DNA methylation Cell 1992 70, N 1:5–8.
[61] Feng Q., Balasubramanian A., Hawes S. E., Toure P., Sow P. S., Dem A., Dembele B., Critchlow C. W., Xi L., Lu H., McIntosh M. W., Young A. M., Kiviat N. B. Detection of hypermethylated genes in women with and without cervical neoplasia J. Nat. Cancer Inst 2005 97, N 4:273–282.
[62] Kransdorf E. P., Wang S. Z., Zhu S. Z., Langston T. B., Rupon J. W., Ginder G. D. MBD2 is a critical component of a methyl cytosine-binding protein complex isolated from primary erythroid cells Blood 2006 108, N 8:2836–2845.
[63] Salozhin S. V., Prokhortchouk E. B., Georgiev G. P. Methylation of DNA – one of the major epigenetic markers Biochemistry (Mosc.) 2005 70, N 5:525–532.
[64] Kondo E., Gu Z., Horii A., Fukushige S. The thymine DNA glycosylase MBD4 represses transcription and is associated with methylated p16(INK4a) and hMLH1 genes Mol. Cell Biol 2005 25, N 11:4388–4396.
[65] Hattori M., Sakamoto H., Satoh K., Yamamoto T. DNA demethylase is expressed in ovarian cancers and the expression correlates with demethylation of CpG sites in the promoter region of c-erbB-2 and survivin genes Cancer Lett 2001 169, N 2:155–164.
[66] Kanai Y., Ushijima S., Nakanishi Y., Hirohashi S. Reduced mRNA expression of the DNA demethylase, MBD2, in human colorectal and stomach cancers Biochem. Biophys. Res. Communs 1999 264, N 3:962–966.
[67] Baylin S. B., Herman J. G., Graff J. R., Vertino P. M., Issa J. P. Alterations in DNA methylation: a fundamental aspect of neoplasia Adv. Cancer Res 1998 72:141–196.
[68] Mummaneni P., Yates P., Simpson J., Rose J., Turker M. S. The primary function of a redundant Sp1 binding site in the mouse aprt gene promoter is to block epigenetic gene inactivation Nucl. Acids Res 1998 26, N 22:5163–5169.
[69] Lujambio A., Calin G. A., Villanueva A., Ropero S., SanchezCespedes M., Blanco D., Montuenga L. M., Rossi S., Nicoloso M. S., Faller W. J., Gallagher W. M., Eccles S. A., Croce C. M., Esteller M. A microRNA DNA methylation signature for human cancer metastasis Proc. Natl Acad. Sci. USA 2008 105, N 36:13556–13561.
[70] Szyf M. DNA methylation and demethylation as targets for anticancer therapy Biochemistry (Mosc) 2005 70, N 5:533–549.
[71] Ye F., Zhang S. F., Xie X., Lu W. G. OPCML gene promoter methylation and gene expression in tumor and stroma cells of invasive cervical carcinoma Cancer Invest 2008 26, N 6:569–574.
[72] Overmeer R. M., Henken F. E., Snijders P. J., Claassen-Kramer D., Berkhof J., Helmerhorst T. J., Heideman D. A., Wilting S. M., Murakami Y., Ito A., Meijer C. J., Steenbergen R. D. Association between dense CADM1 promoter methylation and reduced protein expression in high-grade CIN and cervical SCC J. Pathol 2008 215, N 4:388–397.
[73] Lee J., Yoon Y. S., Chung J. H. Epigenetic silencing of the WNT antagonist DICKKOPF-1 in cervical cancer cell lines Gynecol. Oncol 2008 109,–N 2:270–274.
[74] Lim S. L., Smith P., Syed N., Coens C., Wong H., van der Burg M., Szlosarek P., Crook T., Green J. A. Promoter hypermethylation of FANCF and outcome in advanced ovarian cancer Br. J. Cancer 2008 98, N 8:1452–1456.
[75] Mhawech P., Benz A., Cerato C., Greloz V., Assaly M., Desmond J. C., Koeffler H. P., Lodygin D., Hermeking H., Herrmann F., Schwaller J. Downregulation of 14-3-3sigma in ovary, prostate and endometrial carcinomas is associated with CpG island methylation Mod. Pathol 2005 18, N 3:340–348.
[76] Feng W., Marquez R. T., Lu Z., Liu J., Lu K. H., Issa J. P., Fishman D. M., Yu Y., Bast R. C. Jr. Imprinted tumor suppressor genes ARHI and PEG3 are the most frequently downregulated in human ovarian cancers by loss of heterozygosity and promoter methylation Cancer 2008 112, N 7:1489–1502.
[77] Chen H., Ye F., Zhang J., Lu W., Cheng Q., Xie X. Loss of OPCML expression and the correlation with CpG island methylation and LOH in ovarian serous carcinoma Eur. J. Gynaecol. Oncol 2007 28, N 6:464–467.
[78] Teodoridis J. M., Hall J., Marsh S., Kannall H. D., Smyth C., Curto J., Siddiqui N., Gabra H., McLeod H. L., Strathdee G., Brown R. CpG island methylation of DNA damage response genes in advanced ovarian cancer Cancer Res 2005 65, N 19:8961–8967.
[79] Kwong J., Lee J. Y., Wong K. K., Zhou X., Wong D. T., Lo K. W., Welch W. R., Berkowitz R. S., Mok S. C. Candidate tumor-suppressor gene DLEC1 is frequently downregulated by promoter hypermethylation and histone hypoacetylation in human epithelial ovarian cancer Neoplasia 2006 8, N 4:268–278.
[80] Agathanggelou A., Honorio S., Macartney D. P., Martinez A., Dallol A., Rader J., Fullwood P., Chauhan A., Walker R., Shaw J. A., Hosoe S., Lerman M. I., Minna J. D., Maher E. R., Latif F. Methylation associated inactivation of RASSF1A from region 3p21.3 in lung, breast and ovarian tumours Oncogene 2001 20, N 12:1509–1518.
[81] Maat W., Ly L. V., Jordanova E. S., de Wolff-Rouendaal D., Schalij-Delfos N. E., Jager M. J. Monosomy of chromosome 3 and an inflammatory phenotype occur together in uveal melanoma Invest. Ophthalmol. Vis. Sci 2008 49, N 2:505–510.
[82] Vidaurreta M., Maestro M. L., Sanz-Casla M. T., Maestro C., Rafael S., Veganzones S., Moreno J., Blanco J., Silmi A., Arroyo M. Inactivation of p16 by CpG hypermethylation in renal cell carcinoma Urol. Oncol 2008 26, N 3:239– 245.
[83] Majid S., Dar A. A., Shahryari V., Hirata H., Ahmad A., Saini S., Tanaka Y., Dahiya A. V., Dahiya R. Genistein reverses hypermethylation and induces active histone modifications in tumor suppressor gene B-Cell translocation gene 3 in prostate cancer Cancer 2010 116, N1:66–76.
[84] Majid S., Dar A. A., Ahmad A. E., Hirata H., Kawakami K., Shahryari V., Saini S., Tanaka Y., Dahiya A. V., Khatri G., Dahiya R. BTG3 tumor suppressor gene promoter demethylation, histone modification and cell cycle arrest by genistein in renal cancer Carcinogenesis 2009 30, N 4:662– 670.
[85] Lu T. Y., Kao C. F., Lin C. T., Huang D. Y., Chiu C. Y., Huang Y. S., Wu H. C. DNA methylation and histone modification regulate silencing of OPG during tumor progression J. Cell Biochem 2009 108, N 1:315–325.
[86] Kaneuchi M., Sasaki M., Tanaka Y., Shiina H., Verma M., Ebina Y., Nomura E., Yamamoto R., Sakuragi N., Dahiya R. Expression and methylation status of 14-3-3 sigma gene can characterize the different histological features of ovarian cancer Biochem. Biophys. Res. Communs 2004 316, N 4:1156–1162.
[87] Terasawa K., Sagae S., Toyota M., Tsukada K., Ogi K., Satoh A., Mita H., Imai K., Tokino T., Kudo R. Epigenetic inactivation of TMS1/ASC in ovarian cancer Clin. Cancer Res 2004 10, N 6:2000–2006.
[88] Kaneuchi M., Sasaki M., Tanaka Y., Shiina H., Yamada H., Yamamoto R., Sakuragi N., Enokida H., Verma M., Dahiya R. WT1 and WT1-AS genes are inactivated by promoter methylation in ovarian clear cell adenocarcinoma Cancer 2005 104, N 9:1924–1930.
[89] Makarla P. B., Saboorian M. H., Ashfaq R., Toyooka K. O., Toyooka S., Minna J. D., Gazdar A. F., Schorge J. O. Promoter hypermethylation profile of ovarian epithelial neoplasms Clin. Cancer Res 2005 11, N 15:5365–5369.
[90] Richiardi L., Fiano V., Vizzini L., De Marco L., Delsedime L., Akre O., Tos A. G., Merletti F. Promoter methylation in APC, RUNX3, and GSTP1 and mortality in prostate cancer patients J. Clin. Oncol 2009 27, N 19:3161–3168.
[91] Wilson A. S., Power B. E., Molloy P. L. DNA hypomethylation and human diseases Biochim. Biophys. Acta 2007 1775, N 1:138–162.
[92] Ehrlich M. DNA methylation and cancer-associated genetic instability Adv. Exp. Med. Biol 2005 570. –P. 363–392.
[93] Del Senno L., Maestri I., Piva R., Hanau S., Reggiani A., Romano A., Russo G. Differential hypomethylation of the c-myc protooncogene in bladder cancers at different stages and grades J. Urol 1989 142, N 1:146–149.
[94] Izutsu N., Maesawa C., Shibazaki M., Oikawa H., Shoji T., Sugiyama T., Masuda T. Epigenetic modification is involved in aberrant expression of class III beta-tubulin, TUBB3, in ovarian cancer cells Int. J. Oncol 2008 32, N 6:1227–1235.
[95] Rose S. L., Fitzgerald M. P., White N. O., Hitchler M. J., Futscher B. W., De Geest K., Domann F. E. Epigenetic regulation of maspin expression in human ovarian carcinoma cells Gynecol. Oncol 2006 102, N 2:319–324.
[96] Czekierdowski A., Czekierdowska S., Wielgos M., Smolen A., Kaminski P., Kotarski J. The role of CpG islands hypomethylation and abnormal expression of neuronal protein synuclein-gamma (SNCG) in ovarian cancer. Neuro Endocrinol. Lett. 2006; 27(3):381–386.
[97] Litkouhi B., Kwong J., Lo C. M., Smedley J. G. 3rd., McClane B. A., Aponte M., Gao Z., Sarno J. L., Hinners J., Welch W. R., Berkowitz R. S., Mok S. C., Garner E. I. Claudin-4 overexpression in epithelial ovarian cancer is associated with hypomethylation and is a potential target for modulation of tight junction barrier function using a C-terminal fragment of Clostridium perfringens enterotoxin Neoplasia 2007 9, N 4:304–314.
[98] Florl A. R., Lower R., Schmitz-Drager B. J., Schulz W. A. DNA methylation and expression of LINE-1 and HERV-K provirus sequences in urothelial and renal cell carcinomas Br. J. Cancer 1999 80, N 9:1312–1321.
[99] Widschwendter M., Siegmund K. D., Muller H. M., Fiegl H., Marth C., Muller-Holzner E., Jones P. A., Laird P. W. Association of breast cancer DNA methylation profiles with hormone receptor status and response to tamoxifen Cancer Res 2004 64, N 11:3807–3813.
[100] Poleshko A., Einarson M. B., Shalginskikh N., Zhang R., Adams P. D., Skalka A. M., Katz R. A. Identification of a functional network of human epigenetic silencing factors J. Biol. Chem 2010 285, N 1:422–433.