, Volume 19, Issue 2, pp 298–305 | Cite as

Transcription control of DAPK

  • Natalya Benderska
  • Regine Schneider-StockEmail author
The Universe of DAPK


Imbalanced cell death is a common phenomenon in many human diseases, including cancer. DAPK′s essential function is in promoting apoptosis. DAPK interacts with stress-induced receptors through its death domain to initiate an apoptosis cascade. In addition, DAPK phosphorylates multiple cytosolic substrates and can mediate transfer of signaling pathways to the effector caspases. A series of studies demonstrated that, depending on stimuli, DAPK expression is regulated on both the transcriptional and posttranscriptional levels. Silencing of DAPK due to hypermethylation of its promoter was reported in many types of cancer. STAT3 and p52-NFkB transcription factors have been shown to down-regulate DAPK expression. In contrast, p53, C/EBP-β and Smad transcription factors bind to their specific response elements within the DAPK promoter and induce its transcription. Post-transcriptionally, DAPK undergoes alternative splicing, which results in the production of two functionally different isoforms. Moreover, miRNA 103 and miRNA 107 recently were shown to inhibit DAPK in colorectal cancer. Here we summarize our recent knowledge about transcriptional regulation of DAPK expression.


DAPK Transcription factor Methylation Cancer Apoptosis 



The work in RSS′s Lab is supported by Deutsche Forschungsgemeinschaft grants (SCHN477-9-2 to R.SS.), Manfred-Stolte Stiftung (38736003, 38736005, 38736007 to R.SS.) and Interdisciplinary Centre for Clinical Research (IZKF-D18 to R.SS).


  1. 1.
    Deiss LP, Feinstein E, Berissi H, Cohen O, Kimchi A (1995) Identification of a novel serine/threonine kinase and a novel 15-kD protein as potential mediators of the gamma interferon-induced cell death. Genes Dev 9(1):15–30PubMedCrossRefGoogle Scholar
  2. 2.
    Inbal B, Cohen O, Polak-Charcon S, Kopolovic J, Vadai E, Eisenbach L, Kimchi A (1997) DAP kinase links the control of apoptosis to metastasis. Nature 390(6656):180–184. doi: 10.1038/36599 PubMedCrossRefGoogle Scholar
  3. 3.
    Cohen O, Inbal B, Kissil JL, Raveh T, Berissi H, Spivak-Kroizaman T, Feinstein E, Kimchi A (1999) DAP-kinase participates in TNF-alpha- and Fas-induced apoptosis and its function requires the death domain. J Cell Biol 146(1):141–148PubMedCrossRefGoogle Scholar
  4. 4.
    Jang CW, Chen CH, Chen CC, Chen JY, Su YH, Chen RH (2002) TGF-beta induces apoptosis through Smad-mediated expression of DAP-kinase. Nature cell biology 4(1):51–58. doi: 10.1038/ncb731ncb731 PubMedCrossRefGoogle Scholar
  5. 5.
    Chen T, Li E (2004) Structure and function of eukaryotic DNA methyltransferases. Current topics in developmental biology 60:55–89. doi: 10.1016/S0070-2153(04)60003-2 PubMedGoogle Scholar
  6. 6.
    Gardiner-Garden M, Frommer M (1987) CpG islands in vertebrate genomes. J Mol Biol 196(2):261–282PubMedCrossRefGoogle Scholar
  7. 7.
    Antequera F, Bird A (1993) Number of CpG islands and genes in human and mouse. Proc Natl Acad Sci USA 90(24):11995–11999PubMedCrossRefGoogle Scholar
  8. 8.
    Cross SH, Bird AP (1995) CpG islands and genes. Curr Opin Genet Dev 5(3):309–314PubMedCrossRefGoogle Scholar
  9. 9.
    Wutz A, Smrzka OW, Schweifer N, Schellander K, Wagner EF, Barlow DP (1997) Imprinted expression of the Igf2r gene depends on an intronic CpG island. Nature 389(6652):745–749. doi: 10.1038/39631 PubMedCrossRefGoogle Scholar
  10. 10.
    Lee JT (2003) Molecular links between X-inactivation and autosomal imprinting: X-inactivation as a driving force for the evolution of imprinting? Curr Biol 13(6):R242–R254PubMedCrossRefGoogle Scholar
  11. 11.
    Feinberg AP, Tycko B (2004) The history of cancer epigenetics. Nat Rev Cancer 4(2):143–153. doi: 10.1038/nrc1279 PubMedCrossRefGoogle Scholar
  12. 12.
    Pulling LC, Grimes MJ, Damiani LA, Juri DE, Do K, Tellez CS, Belinsky SA (2009) Dual promoter regulation of death-associated protein kinase gene leads to differentially silenced transcripts by methylation in cancer. Carcinogenesis 30(12):2023–2030. doi: 10.1093/carcin/bgp276 PubMedCrossRefGoogle Scholar
  13. 13.
    Kuester D, Guenther T, Biesold S, Hartmann A, Bataille F, Ruemmele P, Peters B, Meyer F, Schubert D, Bohr UR, Malfertheiner P, Lippert H, Silver AR, Roessner A, Schneider-Stock R (2010) Aberrant methylation of DAPK in long-standing ulcerative colitis and ulcerative colitis-associated carcinoma. Pathol Res Pract 206(9):616–624. doi: 10.1016/j.prp.2010.05.004 PubMedCrossRefGoogle Scholar
  14. 14.
    Chakilam S, Gandesiri M, Rau TT, Agaimy A, Vijayalakshmi M, Ivanovska J, Wirtz RM, Schulze-Luehrmann J, Benderska N, Wittkopf N, Chellappan A, Ruemmele P, Vieth M, Rave-Frank M, Christiansen H, Hartmann A, Neufert C, Atreya R, Becker C, Steinberg P, Schneider-Stock R (2013) Death-associated protein kinase controls STAT3 activity in intestinal epithelial cells. Am J Pathol 182(3):1005–1020. doi: 10.1016/j.ajpath.2012.11.026 PubMedCrossRefGoogle Scholar
  15. 15.
    Mittag F, Kuester D, Vieth M, Peters B, Stolte B, Roessner A, Schneider-Stock R (2006) DAPK promotor methylation is an early event in colorectal carcinogenesis. Cancer Lett 240(1):69–75. doi: 10.1016/j.canlet.2005.08.034 PubMedCrossRefGoogle Scholar
  16. 16.
    Brait M, Loyo M, Rosenbaum E, Ostrow KL, Markova A, Papagerakis S, Zahurak M, Goodman SM, Zeiger M, Sidransky D, Umbricht CB, Hoque MO (2012) Correlation between BRAF mutation and promoter methylation of TIMP3, RARbeta2 and RASSF1A in thyroid cancer. Epigenetics 7(7):710–719. doi: 10.4161/epi.20524 PubMedCrossRefGoogle Scholar
  17. 17.
    Kissil JL, Feinstein E, Cohen O, Jones PA, Tsai YC, Knowles MA, Eydmann ME, Kimchi A (1997) DAP-kinase loss of expression in various carcinoma and B-cell lymphoma cell lines: possible implications for role as tumor suppressor gene. Oncogene 15(4):403–407. doi: 10.1038/sj.onc.1201172 PubMedCrossRefGoogle Scholar
  18. 18.
    Ng MH (2002) Death associated protein kinase: from regulation of apoptosis to tumor suppressive functions and B cell malignancies. Apoptosis 7(3):261–270PubMedCrossRefGoogle Scholar
  19. 19.
    Reddy AN, Jiang WW, Kim M, Benoit N, Taylor R, Clinger J, Sidransky D, Califano JA (2003) Death-associated protein kinase promoter hypermethylation in normal human lymphocytes. Cancer Res 63(22):7694–7698PubMedGoogle Scholar
  20. 20.
    Brabender J, Arbab D, Huan X, Vallbohmer D, Grimminger P, Ling F, Neiss S, Bollschweiler E, Schneider PM, Holscher AH, Metzger R (2009) Death-associated protein kinase (DAPK) promoter methylation and response to neoadjuvant radiochemotherapy in esophageal cancer. Ann Surg Oncol 16(5):1378–1383. doi: 10.1245/s10434-009-0356-1 PubMedCrossRefGoogle Scholar
  21. 21.
    Kaufmann SH, Earnshaw WC (2000) Induction of apoptosis by cancer chemotherapy. Exp Cell Res 256(1):42–49. doi: 10.1006/excr.2000.4838 PubMedCrossRefGoogle Scholar
  22. 22.
    Tang X, Khuri FR, Lee JJ, Kemp BL, Liu D, Hong WK, Mao L (2000) Hypermethylation of the death-associated protein (DAP) kinase promoter and aggressiveness in stage I non-small-cell lung cancer. J Natl Cancer Inst 92(18):1511–1516PubMedCrossRefGoogle Scholar
  23. 23.
    Kim DH, Nelson HH, Wiencke JK, Christiani DC, Wain JC, Mark EJ, Kelsey KT (2001) Promoter methylation of DAP-kinase: association with advanced stage in non-small cell lung cancer. Oncogene 20(14):1765–1770. doi: 10.1038/sj.onc.1204302 PubMedCrossRefGoogle Scholar
  24. 24.
    Levy D, Plu-Bureau G, Decroix Y, Hugol D, Rostene W, Kimchi A, Gompel A (2004) Death-associated protein kinase loss of expression is a new marker for breast cancer prognosis. Clin Cancer Res 10(9):3124–3130PubMedCrossRefGoogle Scholar
  25. 25.
    Sanchez-Cespedes M, Esteller M, Wu L, Nawroz-Danish H, Yoo GH, Koch WM, Jen J, Herman JG, Sidransky D (2000) Gene promoter hypermethylation in tumors and serum of head and neck cancer patients. Cancer Res 60(4):892–895PubMedGoogle Scholar
  26. 26.
    Puto LA, Reed JC (2008) Daxx represses RelB target promoters via DNA methyltransferase recruitment and DNA hypermethylation. Genes Dev 22(8):998–1010. doi: 10.1101/gad.1632208 PubMedCrossRefGoogle Scholar
  27. 27.
    Bialik S, Kimchi A (2006) The death-associated protein kinases: structure, function, and beyond. Annu Rev Biochem 75:189–210. doi: 10.1146/annurev.biochem.75.103004.142615 PubMedCrossRefGoogle Scholar
  28. 28.
    Raval A, Tanner SM, Byrd JC, Angerman EB, Perko JD, Chen SS, Hackanson B, Grever MR, Lucas DM, Matkovic JJ, Lin TS, Kipps TJ, Murray F, Weisenburger D, Sanger W, Lynch J, Watson P, Jansen M, Yoshinaga Y, Rosenquist R, de Jong PJ, Coggill P, Beck S, Lynch H, de la Chapelle A, Plass C (2007) Downregulation of death-associated protein kinase 1 (DAPK1) in chronic lymphocytic leukemia. Cell 129(5):879–890. doi: 10.1016/j.cell.2007.03.043 PubMedCrossRefGoogle Scholar
  29. 29.
    Martoriati A, Doumont G, Alcalay M, Bellefroid E, Pelicci PG, Marine JC (2005) dapk1, encoding an activator of a p19ARF-p53-mediated apoptotic checkpoint, is a transcription target of p53. Oncogene 24(8):1461–1466. doi: 10.1038/sj.onc.1208256 PubMedCrossRefGoogle Scholar
  30. 30.
    Croniger C, Trus M, Lysek-Stupp K, Cohen H, Liu Y, Darlington GJ, Poli V, Hanson RW, Reshef L (1997) Role of the isoforms of CCAAT/enhancer-binding protein in the initiation of phosphoenolpyruvate carboxykinase (GTP) gene transcription at birth. J Biol Chem 272(42):26306–26312PubMedCrossRefGoogle Scholar
  31. 31.
    Darlington GJ, Ross SE, MacDougald OA (1998) The role of C/EBP genes in adipocyte differentiation. J Biol Chem 273(46):30057–30060PubMedCrossRefGoogle Scholar
  32. 32.
    Seagroves TN, Krnacik S, Raught B, Gay J, Burgess-Beusse B, Darlington GJ, Rosen JM (1998) C/EBPbeta, but not C/EBPalpha, is essential for ductal morphogenesis, lobuloalveolar proliferation, and functional differentiation in the mouse mammary gland. Genes Dev 12(12):1917–1928PubMedCrossRefGoogle Scholar
  33. 33.
    Poli V (1998) The role of C/EBP isoforms in the control of inflammatory and native immunity functions. J Biol Chem 273(45):29279–29282PubMedCrossRefGoogle Scholar
  34. 34.
    Akira S, Kishimoto T (1997) NF-IL6 and NF-kappa B in cytokine gene regulation. Adv Immunol 65:1–46PubMedCrossRefGoogle Scholar
  35. 35.
    Kalvakolanu DV (2003) Alternate interferon signaling pathways. Pharmacol Ther 100(1):1–29PubMedCrossRefGoogle Scholar
  36. 36.
    Lekstrom-Himes J, Xanthopoulos KG (1998) Biological role of the CCAAT/enhancer-binding protein family of transcription factors. J Biol Chem 273(44):28545–28548PubMedCrossRefGoogle Scholar
  37. 37.
    Gade P, Roy SK, Li H, Nallar SC, Kalvakolanu DV (2008) Critical role for transcription factor C/EBP-beta in regulating the expression of death-associated protein kinase 1. Mol Cell Biol 28(8):2528–2548. doi: 10.1128/MCB.00784-07 PubMedCentralPubMedCrossRefGoogle Scholar
  38. 38.
    Anjum R, Roux PP, Ballif BA, Gygi SP, Blenis J (2005) The tumor suppressor DAP kinase is a target of RSK-mediated survival signaling. Curr Biol 15(19):1762–1767. doi: 10.1016/j.cub.2005.08.050 PubMedCrossRefGoogle Scholar
  39. 39.
    Chen CH, Wang WJ, Kuo JC, Tsai HC, Lin JR, Chang ZF, Chen RH (2005) Bidirectional signals transduced by DAPK-ERK interaction promote the apoptotic effect of DAPK. EMBO J 24(2):294–304. doi: 760051010.1038/sj.emboj.7600510 PubMedCrossRefGoogle Scholar
  40. 40.
    Massague J, Seoane J, Wotton D (2005) Smad transcription factors. Genes Dev 19(23):2783–2810. doi: 10.1101/gad.1350705 PubMedCrossRefGoogle Scholar
  41. 41.
    Shanmugam R, Gade P, Wilson-Weekes A, Sayar H, Suvannasankha A, Goswami C, Li L, Gupta S, Cardoso AA, Al Baghdadi T, Sargent KJ, Cripe LD, Kalvakolanu DV, Boswell HS (2012) A noncanonical Flt3ITD/NF-kappaB signaling pathway represses DAPK1 in acute myeloid leukemia. Clin Cancer Res 18(2):360–369. doi: 10.1158/1078-0432.CCR-10-3022 PubMedCrossRefGoogle Scholar
  42. 42.
    Hayakawa J, Mittal S, Wang Y, Korkmaz KS, Adamson E, English C, Ohmichi M, McClelland M, Mercola D (2004) Identification of promoters bound by c-Jun/ATF2 during rapid large-scale gene activation following genotoxic stress. Mol Cell 16(4):521–535. doi: 10.1016/j.molcel.2004.10.024 PubMedCrossRefGoogle Scholar
  43. 43.
    Barberan-Soler S, Zahler AM (2008) Alternative splicing regulation during C. elegans development: splicing factors as regulated targets. PLoS Genetics 4(2):e1000001. doi: 10.1371/journal.pgen.1000001 PubMedCentralPubMedCrossRefGoogle Scholar
  44. 44.
    Kornblihtt AR (2007) Coupling transcription and alternative splicing. Adv Exp Med Biol 623:175–189PubMedCrossRefGoogle Scholar
  45. 45.
    Grabowski PJ, Black DL (2001) Alternative RNA splicing in the nervous system. Prog Neurobiol 65(3):289–308PubMedCrossRefGoogle Scholar
  46. 46.
    Stamm S (2002) Signals and their transduction pathways regulating alternative splicing: a new dimension of the human genome. Hum Mol Genet 11(20):2409–2416PubMedCrossRefGoogle Scholar
  47. 47.
    Pick M, Flores-Flores C, Soreq H (2004) From brain to blood: alternative splicing evidence for the cholinergic basis of Mammalian stress responses. Ann N Y Acad Sci 1018:85–98. doi: 10.1196/annals.1296.010 PubMedCrossRefGoogle Scholar
  48. 48.
    Jin Y, Gallagher PJ (2003) Antisense depletion of death-associated protein kinase promotes apoptosis. J Biol Chem 278(51):51587–51593. doi: 10.1074/jbc.M309165200 PubMedCentralPubMedCrossRefGoogle Scholar
  49. 49.
    Jin Y, Blue EK, Gallagher PJ (2006) Control of death-associated protein kinase (DAPK) activity by phosphorylation and proteasomal degradation. J Biol Chem 281(51):39033–39040. doi: 10.1074/jbc.M605097200 PubMedCentralPubMedCrossRefGoogle Scholar
  50. 50.
    Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116(2):281–297PubMedCrossRefGoogle Scholar
  51. 51.
    He L, Hannon GJ (2004) MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet 5(7):522–531. doi: 10.1038/nrg1379 PubMedCrossRefGoogle Scholar
  52. 52.
    Chen HY, Lin YM, Chung HC, Lang YD, Lin CJ, Huang J, Wang WC, Lin FM, Chen Z, Huang HD, Shyy JY, Liang JT, Chen RH (2012) miR-103/107 promote metastasis of colorectal cancer by targeting the metastasis suppressors DAPK and KLF4. Cancer Res 72(14):3631–3641. doi: 10.1158/0008-5472.CAN-12-0667 PubMedCrossRefGoogle Scholar
  53. 53.
    Merhavi E, Cohen Y, Avraham BC, Frenkel S, Chowers I, Pe’er J, Goldenberg-Cohen N (2007) Promoter methylation status of multiple genes in uveal melanoma. Invest Ophthalmol Vis Sci 48(10):4403–4406. doi: 10.1167/iovs.07-0272 PubMedCrossRefGoogle Scholar
  54. 54.
    Hou P, Ji M, Yang B, Chen Z, Qiu J, Shi X, Lu Z (2006) Quantitative analysis of promoter hypermethylation in multiple genes in osteosarcoma. Cancer 106(7):1602–1609. doi: 10.1002/cncr.21762 PubMedCrossRefGoogle Scholar
  55. 55.
    Esteller M, Corn PG, Baylin SB, Herman JG (2001) A gene hypermethylation profile of human cancer. Cancer Res 61(8):3225–3229PubMedGoogle Scholar
  56. 56.
    Roman-Gomez J, Jimenez-Velasco A, Castillejo JA, Agirre X, Barrios M, Navarro G, Molina FJ, Calasanz MJ, Prosper F, Heiniger A, Torres A (2004) Promoter hypermethylation of cancer-related genes: a strong independent prognostic factor in acute lymphoblastic leukemia. Blood 104(8):2492–2498. doi: 10.1182/blood-2004-03-0954 PubMedCrossRefGoogle Scholar
  57. 57.
    Gao Y, Guan M, Su B, Liu W, Xu M, Lu Y (2004) Hypermethylation of the RASSF1A gene in gliomas. Clinica Chimica Acta 349(1–2):173–179. doi: 10.1016/j.cccn.2004.07.006 CrossRefGoogle Scholar
  58. 58.
    Xiaofang L, Kun T, Shaoping Y, Zaiqiu W, Hailong S (2012) Correlation between promoter methylation of p14(ARF), TMS1/ASC, and DAPK, and p53 mutation with prognosis in cholangiocarcinoma. World J Surg Oncol 10:5. doi: 10.1186/1477-7819-10-5 PubMedCentralPubMedCrossRefGoogle Scholar
  59. 59.
    Hoon DS, Spugnardi M, Kuo C, Huang SK, Morton DL, Taback B (2004) Profiling epigenetic inactivation of tumor suppressor genes in tumors and plasma from cutaneous melanoma patients. Oncogene 23(22):4014–4022. doi: 10.1038/sj.onc.1207505 PubMedCentralPubMedCrossRefGoogle Scholar
  60. 60.
    Rastetter M, Schagdarsurengin U, Lahtz C, Fiedler E, Marsch W, Dammann R, Helmbold P (2007) Frequent intra-tumoural heterogeneity of promoter hypermethylation in malignant melanoma. Histol Histopathol 22(9):1005–1015PubMedGoogle Scholar
  61. 61.
    Maruyama R, Toyooka S, Toyooka KO, Virmani AK, Zochbauer-Muller S, Farinas AJ, Minna JD, McConnell J, Frenkel EP, Gazdar AF (2002) Aberrant promoter methylation profile of prostate cancers and its relationship to clinicopathological features. Clin Cancer Res 8(2):514–519PubMedGoogle Scholar
  62. 62.
    Yamanaka M, Watanabe M, Yamada Y, Takagi A, Murata T, Takahashi H, Suzuki H, Ito H, Tsukino H, Katoh T, Sugimura Y, Shiraishi T (2003) Altered methylation of multiple genes in carcinogenesis of the prostate. Int J Cancer 106(3):382–387. doi: 10.1002/ijc.11227 PubMedCrossRefGoogle Scholar
  63. 63.
    Lin HY, Huang TT, Lee MS, Hung SK, Lin RI, Tseng CE, Chang SM, Chiou WY, Hsu FC, Hsu WL, Liu DW, Su YC, Li SC, Chan MW (2013) Unexpected close surgical margin in resected buccal cancer: very close margin and DAPK promoter hypermethylation predict poor clinical outcomes. Oral Oncology 49(4):336–344. doi: 10.1016/j.oraloncology.2012.11.005 PubMedCrossRefGoogle Scholar
  64. 64.
    Hafner N, Diebolder H, Jansen L, Hoppe I, Durst M, Runnebaum IB (2011) Hypermethylated DAPK in serum DNA of women with uterine leiomyoma is a biomarker not restricted to cancer. Gynecol Oncol 121(1):224–229. doi: 10.1016/j.ygyno.2010.11.018 PubMedCrossRefGoogle Scholar
  65. 65.
    Wu LM, Zhang F, Zhou L, Yang Z, Xie HY, Zheng SS (2010) Predictive value of CpG island methylator phenotype for tumor recurrence in hepatitis B virus-associated hepatocellular carcinoma following liver transplantation. BMC Cancer 10:399. doi: 10.1186/1471-2407-10-399 PubMedCentralPubMedCrossRefGoogle Scholar
  66. 66.
    Sugita H, Iida S, Inokuchi M, Kato K, Ishiguro M, Ishikawa T, Takagi Y, Enjoji M, Yamada H, Uetake H, Kojima K, Sugihara K (2011) Methylation of BNIP3 and DAPK indicates lower response to chemotherapy and poor prognosis in gastric cancer. Oncol Rep 25(2):513–518. doi: 10.3892/or.2010.1085 PubMedCrossRefGoogle Scholar
  67. 67.
    Ben Ayed-Guerfali D, Benhaj K, Khabir A, Abid M, Bayrouti MI, Sellami-Boudawara T, Gargouri A, Mokdad-Gargouri R (2011) Hypermethylation of tumor-related genes in Tunisian patients with gastric carcinoma: clinical and biological significance. J Surg Oncol 103(7):687–694. doi: 10.1002/jso.21875 PubMedCrossRefGoogle Scholar
  68. 68.
    Peng Z, Shan C, Wang H (2010) Value of promoter methylation of RASSF1A, p16, and DAPK genes in induced sputum in diagnosing lung cancers. Zhong Nan Da Xue Xue Bao Yi Xue Ban 35(3):247–253. doi: 10.3969/j.issn.1672-7347.2010.03.010 PubMedGoogle Scholar
  69. 69.
    Narayan G, Arias-Pulido H, Koul S, Vargas H, Zhang FF, Villella J, Schneider A, Terry MB, Mansukhani M, Murty VV (2003) Frequent promoter methylation of CDH1, DAPK, RARB, and HIC1 genes in carcinoma of cervix uteri: its relationship to clinical outcome. Mol Cancer 2:24PubMedCentralPubMedCrossRefGoogle Scholar
  70. 70.
    Niyazi M, Liu XW, Zhu KC (2012) Death-associated protein kinase promoter (DAPK) hypermethylation in uterine cervical cancer and intraepithelial neoplasia in Uyghur nationality women. Zhonghua zhong liu za zhi [Chinese journal of oncology] 34(1):31–34Google Scholar
  71. 71.
    Christoph F, Weikert S, Kempkensteffen C, Krause H, Schostak M, Kollermann J, Miller K, Schrader M (2006) Promoter hypermethylation profile of kidney cancer with new proapoptotic p53 target genes and clinical implications. Clin Cancer Res 12(17):5040–5046. doi: 10.1158/1078-0432.CCR-06-0144 PubMedCrossRefGoogle Scholar
  72. 72.
    Ahmad ST, Arjumand W, Seth A, Saini AK, Sultana S (2012) Methylation of the APAF-1 and DAPK-1 promoter region correlates with progression of renal cell carcinoma in North Indian population. Tumour Biol 33(2):395–402. doi: 10.1007/s13277-011-0235-9 PubMedCrossRefGoogle Scholar
  73. 73.
    Jing F, Yuping W, Yong C, Jie L, Jun L, Xuanbing T, Lihua H (2010) CpG island methylator phenotype of multigene in serum of sporadic breast carcinoma. Tumour Biol 31(4):321–331. doi: 10.1007/s13277-010-0040-x PubMedCrossRefGoogle Scholar
  74. 74.
    Botezatu A, Goia-Rusanu CD, Iancu IV, Huica I, Plesa A, Socolov D, Ungureanu C, Anton G (2011) Quantitative analysis of the relationship between microRNA124a, -34b and -203 gene methylation and cervical oncogenesis. Mol Med Rep 4(1):121–128. doi: 10.3892/mmr.2010.394 PubMedGoogle Scholar
  75. 75.
    Jablonowski Z, Reszka E, Gromadzinska J, Wasowicz W, Sosnowski M (2011) Hypermethylation of p16 and DAPK promoter gene regions in patients with non-invasive urinary bladder cancer. Arch Med Sci 7(3):512–516. doi: 10.5114/aoms.2011.23421 PubMedCentralPubMedCrossRefGoogle Scholar
  76. 76.
    Sun W, Zaboli D, Wang H, Liu Y, Arnaoutakis D, Khan T, Khan Z, Koch WM, Califano JA (2012) Detection of TIMP3 promoter hypermethylation in salivary rinse as an independent predictor of local recurrence-free survival in head and neck cancer. Clin Cancer Res 18(4):1082–1091. doi: 10.1158/1078-0432.CCR-11-2392 PubMedCentralPubMedCrossRefGoogle Scholar
  77. 77.
    Steinmann K, Sandner A, Schagdarsurengin U, Dammann RH (2009) Frequent promoter hypermethylation of tumor-related genes in head and neck squamous cell carcinoma. Oncol Rep 22(6):1519–1526PubMedGoogle Scholar
  78. 78.
    Krajnovic M, Radojkovic M, Davidovic R, Dimitrijevic B, Krtolica K (2013) Prognostic significance of epigenetic inactivation of p16, p15, MGMT and DAPK genes in follicular lymphoma. Med Oncol 30(1):441. doi: 10.1007/s12032-012-0441-3 PubMedCrossRefGoogle Scholar
  79. 79.
    Kim JC, Choi JS, Roh SA, Cho DH, Kim TW, Kim YS (2010) Promoter methylation of specific genes is associated with the phenotype and progression of colorectal adenocarcinomas. Ann Surg Oncol 17(7):1767–1776. doi: 10.1245/s10434-009-0901-y PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Experimental Tumorpathology, Institute of PathologyFriedrich-Alexander- University of Erlangen-NurembergErlangenGermany

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