Skip to main content

Advertisement

SpringerLink
Log in

DNA hypermethylation biomarkers to predict response to cisplatin treatment, radiotherapy or chemoradiation: the present state of art

  • Review
  • Published:
Cellular Oncology Aims and scope Submit manuscript

Abstract

Background

Concurrent platinum-based chemoradiation significantly improved survival of advanced stage cervical patients over radiotherapy alone. However, the 5-year overall survival is still only 66%. Presently, no biomarkers are available to select those cervical cancer patients that might benefit from concurrent platinum-based chemoradiation therapy. DNA methylation is a well-established contributor to the regulation of gene transcription, predominantly causing transcriptional silencing. Differences in promoter hypermethylation patterns and subsequent silencing, could contribute to the variety of responses observed in clinical practice. Several clinical trials on various malignancies reported a better response when Decitabine was administered prior to or in combination with standard therapy. This sensitization is thought to be due to re-expression of tumor suppressor genes. However, not all patients might benefit from demethylating agents, since re-expression of oncogenes could render patients more resistant.

Aim

In this review, we summarized the present state of art regarding hypermethylated genes and their affected signaling pathways that are associated with outcome after cisplatin treatment, radiotherapy or chemoradiation. Since only few studies were reported in cervical cancer, other malignancies were reviewed as well.

Conclusions

From the data presented in this review, we conclude that, in order to select patients that benefit most optimally from demethylating strategies, a comprehensive screening of a large panel of methylation markers, associated with both good as well as poor clinical outcome have to be investigated. Since such panels are not available at this moment, global methylation screening approaches are required to profile such methylated genes. Such methylated gene profiles might be very useful to optimize personalized treatment planning not only in cervical cancer but also in other malignancies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. J. Ferlay, H.R. Shin, F. Bray, D. Forman, C. Mathers, D.M. Parkin, Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 127(12), 2893–2917 (2010)

    Article  PubMed  CAS  Google Scholar 

  2. C. McNeil, New standard of care for cervical cancer sets stage for next questions. J Natl Cancer Inst 91(6), 500–501 (1999)

    Article  PubMed  CAS  Google Scholar 

  3. H.M. Keys, B.N. Bundy, F.B. Stehman, L.I. Muderspach, W.E. Chafe, C.L. Suggs 3rd, J.L. Walker, D. Gersell, Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma. N Engl J Med 340(15), 1154–1161 (1999)

    Article  PubMed  CAS  Google Scholar 

  4. M. Morris, P.J. Eifel, J. Lu, P.W. Grigsby, C. Levenback, R.E. Stevens, M. Rotman, D.M. Gershenson, D.G. Mutch, Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer. N Engl J Med 340(15), 1137–1143 (1999)

    Article  PubMed  CAS  Google Scholar 

  5. C.W. Whitney, W. Sause, B.N. Bundy, J.H. Malfetano, E.V. Hannigan, W.C. Fowler Jr., D.L. Clarke-Pearson, S.Y. Liao, Randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an adjunct to radiation therapy in stage IIB-IVA carcinoma of the cervix with negative para-aortic lymph nodes: a Gynecologic Oncology Group and Southwest Oncology Group study. J Clin Oncol 17(5), 1339–1348 (1999)

    PubMed  CAS  Google Scholar 

  6. W.A. Peters 3rd, P.Y. Liu, R.J. Barrett 2nd, R.J. Stock, B.J. Monk, J.S. Berek, L. Souhami, P. Grigsby, W. Gordon Jr., D.S. Alberts, Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix. J Clin Oncol 18(8), 1606–1613 (2000)

    PubMed  CAS  Google Scholar 

  7. P.G. Rose, B.N. Bundy, E.B. Watkins, J.T. Thigpen, G. Deppe, M.A. Maiman, D.L. Clarke-Pearson, S. Insalaco, Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med 340(15), 1144–1153 (1999)

    Article  PubMed  CAS  Google Scholar 

  8. Chemoradiotherapy for Cervical Cancer Meta-Analysis Collaboration, Reducing Uncertainties About the Effects of Chemoradiotherapy for Cervical Cancer: A Systematic Review and Meta-Analysis of Individual Patient Data From 18 Randomized Trials. J Clin Oncol 26(35), 5802–5812 (2008)

    Google Scholar 

  9. A.W. Fyles, M. Pintilie, P. Kirkbride, W. Levin, L.A. Manchul, G.A. Rawlings, Prognostic factors in patients with cervix cancer treated by radiation therapy: results of a multiple regression analysis. Radiother Oncol 35(2), 107–117 (1995)

    Article  PubMed  CAS  Google Scholar 

  10. A. Jakobsen, P. Bichel, M. Vaeth, New prognostic factors in squamous cell carcinoma of cervix uteri. Am J Clin Oncol 8(1), 39–43 (1985)

    Article  PubMed  CAS  Google Scholar 

  11. D.S. Kapp, D. Fischer, E. Gutierrez, E.I. Kohorn, P.E. Schwartz, Pretreatment prognostic factors in carcinoma of the uterine cervix: a multivariable analysis of the effect of age, stage, histology and blood counts on survival. Int J Radiat Oncol Biol Phys 9(4), 445–455 (1983)

    Article  PubMed  CAS  Google Scholar 

  12. C.A. Perez, P.W. Grigsby, S.M. Nene, H.M. Camel, A. Galakatos, M.S. Kao, M.A. Lockett, Effect of tumor size on the prognosis of carcinoma of the uterine cervix treated with irradiation alone. Cancer 69(11), 2796–2806 (1992)

    Article  PubMed  CAS  Google Scholar 

  13. F.B. Stehman, B.N. Bundy, P.J. DiSaia, H.M. Keys, J.E. Larson, W.C. Fowler, Carcinoma of the cervix treated with radiation therapy. I. A multi-variate analysis of prognostic variables in the Gynecologic Oncology Group. Cancer 67(11), 2776–2785 (1991)

    Article  PubMed  CAS  Google Scholar 

  14. R.A. Cooper, C.M. West, D.P. Wilks, J.P. Logue, S.E. Davidson, S.A. Roberts, R.D. Hunter, Tumour vascularity is a significant prognostic factor for cervix carcinoma treated with radiotherapy: independence from tumour radiosensitivity. Br J Cancer 81(2), 354–358 (1999)

    Article  PubMed  CAS  Google Scholar 

  15. C.M. West, S.E. Davidson, S.A. Roberts, R.D. Hunter, The independence of intrinsic radiosensitivity as a prognostic factor for patient response to radiotherapy of carcinoma of the cervix. Br J Cancer 76(9), 1184–1190 (1997)

    Article  PubMed  CAS  Google Scholar 

  16. T. Toita, Y. Kakinohana, S. Shinzato, K. Ogawa, M. Yoshinaga, S. Iraha, M. Higashi, K. Sakumoto, K. Kanazawa, S. Sawada, Tumor diameter/volume and pelvic node status assessed by magnetic resonance imaging (MRI) for uterine cervical cancer treated with irradiation. Int J Radiat Oncol Biol Phys 43(4), 777–782 (1999)

    Article  PubMed  CAS  Google Scholar 

  17. C.A. Meanwell, K.A. Kelly, S. Wilson, C. Roginski, C. Woodman, R. Griffiths, G. Blackledge, Young age as a prognostic factor in cervical cancer: analysis of population based data from 10,022 cases. Br Med J (Clin Res Ed) 296(6619), 386–391 (1988)

    Article  CAS  Google Scholar 

  18. F.N. Rutledge, M.F. Mitchell, M. Munsell, S. Bass, V. McGuffee, E.N. Atkinson, Youth as a prognostic factor in carcinoma of the cervix: a matched analysis. Gynecol Oncol 44(2), 123–130 (1992)

    Article  PubMed  CAS  Google Scholar 

  19. K.M. Prise, J.M. O’Sullivan, Radiation-induced bystander signalling in cancer therapy. Nat Rev Cancer 9(5), 351–360 (2009)

    Article  PubMed  CAS  Google Scholar 

  20. D. Verellen, M. De Ridder, N. Linthout, K. Tournel, G. Soete, G. Storme, Innovations in image-guided radiotherapy. Nat Rev Cancer 7(12), 949–960 (2007)

    Article  PubMed  CAS  Google Scholar 

  21. M.W. Dewhirst, Y. Cao, B. Moeller, Cycling hypoxia and free radicals regulate angiogenesis and radiotherapy response. Nat Rev Cancer 8(6), 425–437 (2008)

    Article  PubMed  CAS  Google Scholar 

  22. A. Bird, Perceptions of epigenetics. Nature 447(7143), 396–398 (2007)

    Article  PubMed  CAS  Google Scholar 

  23. S.B. Baylin, M. Esteller, M.R. Rountree, K.E. Bachman, K. Schuebel, J.G. Herman, Aberrant patterns of DNA methylation, chromatin formation and gene expression in cancer. Hum Mol Genet 10(7), 687–692 (2001)

    Article  PubMed  CAS  Google Scholar 

  24. S.B. Baylin, J.E. Ohm, Epigenetic gene silencing in cancer - a mechanism for early oncogenic pathway addiction? Nat Rev Cancer 6(2), 107–116 (2006)

    Article  PubMed  CAS  Google Scholar 

  25. J.G. Herman, S.B. Baylin, Gene silencing in cancer in association with promoter hypermethylation. N Engl J Med 349(21), 2042–2054 (2003)

    Article  PubMed  CAS  Google Scholar 

  26. N. Yang, E.R. Nijhuis, H.H. Volders, J.J. Eijsink, A. Lendvai, B. Zhang, H. Hollema, E. Schuuring, G.B. Wisman, A.G. van der Zee, Gene promoter methylation patterns throughout the process of cervical carcinogenesis. Cell Oncol 32(1–2), 131–143 (2010)

    PubMed  CAS  Google Scholar 

  27. G.H. Kang, S. Lee, W.H. Kim, H.W. Lee, J.C. Kim, M.G. Rhyu, J.Y. Ro, Epstein-barr virus-positive gastric carcinoma demonstrates frequent aberrant methylation of multiple genes and constitutes CpG island methylator phenotype-positive gastric carcinoma. Am J Pathol 160(3), 787–794 (2002)

    Article  PubMed  CAS  Google Scholar 

  28. G.H. Kang, S. Lee, N.-Y. Cho, T. Gandamihardja, T.I. Long, D.J. Weisenberger, M. Campan, P.W. Laird, DNA methylation profiles of gastric carcinoma characterized by quantitative DNA methylation analysis. Lab Invest 88(2), 161–170 (2008)

    Article  PubMed  CAS  Google Scholar 

  29. K.L. Richards, B. Zhang, K.A. Baggerly, S. Colella, J.C. Lang, D.E. Schuller, R. Krahe, Genome-wide hypomethylation in head and neck cancer is more pronounced in HPV-negative tumors and is associated with genomic instability. PLoS One 4(3), e4941 (2009)

    Article  PubMed  Google Scholar 

  30. W.A. Burgers, L. Blanchon, S. Pradhan, Y. de Launoit, T. Kouzarides, F. Fuks, Viral oncoproteins target the DNA methyltransferases. Oncogene 26(11), 1650–1655 (2007)

    Article  PubMed  CAS  Google Scholar 

  31. C.B. Yoo, P.A. Jones, Epigenetic therapy of cancer: past, present and future. Nat Rev Drug Discov 5(1), 37–50 (2006)

    Article  PubMed  CAS  Google Scholar 

  32. J.A. Plumb, G. Strathdee, J. Sludden, S.B. Kaye, R. Brown, Reversal of drug resistance in human tumor xenografts by 2′-deoxy-5-azacytidine-induced demethylation of the hMLH1 gene promoter. Cancer Res 60(21), 6039–6044 (2000)

    PubMed  CAS  Google Scholar 

  33. G. Strathdee, M.J. MacKean, M. Illand, R. Brown, A role for methylation of the hMLH1 promoter in loss of hMLH1 expression and drug resistance in ovarian cancer. Oncogene 18(14), 2335–2341 (1999)

    Article  PubMed  CAS  Google Scholar 

  34. F. Fang, C. Balch, J. Schilder, T. Breen, S. Zhang, C. Shen, L. Li, C. Kulesavage, A.J. Snyder, K.P. Nephew, D.E. Matei, A phase 1 and pharmacodynamic study of decitabine in combination with carboplatin in patients with recurrent, platinum-resistant, epithelial ovarian cancer. Cancer 116(17), 4043–4053 (2010)

    Article  PubMed  CAS  Google Scholar 

  35. J.M. Scandura, G.J. Roboz, M. Moh, E.W. Morawa, F. Brenet, J.R. Bose, L. Villegas, U.S. Gergis, S.A. Mayer, C.M. Ippoliti, T.J. Curcio, E.K. Ritchie, E.J. Feldman, Phase I study of epigenetic priming with decitabine prior to standard induction chemotherapy for patients with AML. Blood 118(6), 1472–1480 (2011)

    Article  PubMed  CAS  Google Scholar 

  36. M. Li, C. Balch, J.S. Montgomery, M. Jeong, J.H. Chung, P. Yan, T.H. Huang, S. Kim, K.P. Nephew, Integrated analysis of DNA methylation and gene expression reveals specific signaling pathways associated with platinum resistance in ovarian cancer. BMC Med Genomics 2, 34 (2009)

    Article  PubMed  Google Scholar 

  37. J.P. Issa, V. Gharibyan, J. Cortes, J. Jelinek, G. Morris, S. Verstovsek, M. Talpaz, G. Garcia-Manero, H.M. Kantarjian, Phase II study of low-dose decitabine in patients with chronic myelogenous leukemia resistant to imatinib mesylate. J Clin Oncol 23(17), 3948–3956 (2005)

    Article  PubMed  CAS  Google Scholar 

  38. R.M. Glasspool, M. Gore, G. Rustin, I. McNeish, R. Wilson, S. Pledge, J. Paul, M. Mackean, S. Halford, S. Kaye, Scottish Gynaecological Cancer Trials Group, Randomized phase II study of decitabine in combination with carboplatin compared with carboplatin alone in patients with recurrent advanced ovarian cancer. ASCO Meeting Abstracts 27(15), 5562 (2009)

    Google Scholar 

  39. S.S. Liu, R.C. Leung, K.Y. Chan, P.M. Chiu, A.N. Cheung, K.F. Tam, T.Y. Ng, L.C. Wong, H.Y. Ngan, p73 expression is associated with the cellular radiosensitivity in cervical cancer after radiotherapy. Clin Cancer Res 10(10), 3309–3316 (2004)

    Article  PubMed  CAS  Google Scholar 

  40. G. Narayan, H. Arias-Pulido, S. Koul, H. Vargas, F.F. Zhang, J. Villella, A. Schneider, M.B. Terry, M. Mansukhani, V.V. Murty, Frequent promoter methylation of CDH1, DAPK, RARB, and HIC1 genes in carcinoma of cervix uteri: its relationship to clinical outcome. Mol Cancer 2, 24 (2003)

    Article  PubMed  Google Scholar 

  41. G. Narayan, H. Arias-Pulido, S.V. Nandula, K. Basso, D.D. Sugirtharaj, H. Vargas, M. Mansukhani, J. Villella, L. Meyer, A. Schneider, L. Gissmann, M. Durst, B. Pothuri, V.V. Murty, Promoter hypermethylation of FANCF: disruption of Fanconi Anemia-BRCA pathway in cervical cancer. Cancer Res 64(9), 2994–2997 (2004)

    Article  PubMed  CAS  Google Scholar 

  42. T. Taniguchi, M. Tischkowitz, N. Ameziane, S.V. Hodgson, C.G. Mathew, H. Joenje, S.C. Mok, A.D. D’Andrea, Disruption of the Fanconi anemia-BRCA pathway in cisplatin-sensitive ovarian tumors. Nature Med 9(5), 568–574 (2003)

    Article  PubMed  CAS  Google Scholar 

  43. J.L. Ramirez, R. Rosell, M. Taron, M. Sanchez-Ronco, V. Alberola, Penas R. de Las, J.M. Sanchez, T. Moran, C. Camps, B. Massuti, J.J. Sanchez, F. Salazar, S. Catot, 14-3-3sigma methylation in pretreatment serum circulating DNA of cisplatin-plus-gemcitabine-treated advanced non-small-cell lung cancer patients predicts survival: The Spanish Lung Cancer Group. J Clin Oncol 23(36), 9105–9112 (2005)

    Article  PubMed  CAS  Google Scholar 

  44. M. Zurita, P.C. Lara, R. del Moral, B. Torres, J.L. Linares-Fernandez, S.R. Arrabal, J. Martinez-Galan, F.J. Oliver, J.M. Ruiz de Almodovar, Hypermethylated 14-3-3-sigma and ESR1 gene promoters in serum as candidate biomarkers for the diagnosis and treatment efficacy of breast cancer metastasis. BMC Cancer 10, 217 (2010)

    Article  PubMed  Google Scholar 

  45. P. Chaudhry, R. Srinivasan, F.D. Patel, Utility of gene promoter methylation in prediction of response to platinum-based chemotherapy in epithelial ovarian cancer (EOC). Cancer Invest 27(8), 877–884 (2009)

    Article  PubMed  CAS  Google Scholar 

  46. J.M. Teodoridis, J. Hall, S. Marsh, H.D. Kannall, C. Smyth, J. Curto, N. Siddiqui, H. Gabra, H.L. McLeod, G. Strathdee, R. Brown, CpG island methylation of DNA damage response genes in advanced ovarian cancer. Cancer Res 65(19), 8961–8967 (2005)

    Article  PubMed  CAS  Google Scholar 

  47. Y. Zhang, X. Qu, W. Jing, X. Hu, X. Yang, K. Hou, Y. Teng, J. Zhang, Y. Liu, GSTP1 determines cis-platinum cytotoxicity in gastric adenocarcinoma MGC803 cells: regulation by promoter methylation and extracellular regulated kinase signaling. Anticancer Drugs 20(3), 208–214 (2009)

    Article  PubMed  CAS  Google Scholar 

  48. R.C. Cumming, J. Lightfoot, K. Beard, H. Youssoufian, P.J. O’Brien, M. Buchwald, Fanconi anemia group C protein prevents apoptosis in hematopoietic cells through redox regulation of GSTP1. Nature Med 7(7), 814–820 (2001)

    Article  PubMed  CAS  Google Scholar 

  49. H.Y. Chen, C.J. Shao, F.R. Chen, A.L. Kwan, Z.P. Chen, Role of ERCC1 promoter hypermethylation in drug resistance to cisplatin in human gliomas. Int J Cancer 126(8), 1944–1954 (2010)

    PubMed  CAS  Google Scholar 

  50. W. Wang, Emergence of a DNA-damage response network consisting of Fanconi anaemia and BRCA proteins. Nat Rev Genet 8(10), 735–748 (2007)

    Article  PubMed  CAS  Google Scholar 

  51. K.S. Park, H.K. Kim, J.H. Lee, Y.B. Choi, S.Y. Park, S.H. Yang, S.Y. Kim, K.M. Hong, Transglutaminase 2 as a cisplatin resistance marker in non-small cell lung cancer. J Cancer Res Clin Oncol 136(4), 493–502 (2010)

    Article  PubMed  CAS  Google Scholar 

  52. M. D’Eletto, M.G. Farrace, L. Falasca, V. Reali, S. Oliverio, G. Melino, M. Griffin, G.M. Fimia, M. Piacentini, Transglutaminase 2 is involved in autophagosome maturation. Autophagy 5(8), 1145–1154 (2009)

    Article  PubMed  Google Scholar 

  53. L.J. Nicholson, P.R. Smith, L. Hiller, P.W. Szlosarek, C. Kimberley, J. Sehouli, D. Koensgen, A. Mustea, P. Schmid, T. Crook, Epigenetic silencing of argininosuccinate synthetase confers resistance to platinum-induced cell death but collateral sensitivity to arginine auxotrophy in ovarian cancer. Int J Cancer 125(6), 1454–1463 (2009)

    Article  PubMed  CAS  Google Scholar 

  54. S. Battisti, D. Valente, L. Albonici, R. Bei, A. Modesti, C. Palumbo, Nutritional stress and arginine auxotrophy confer high sensitivity to chloroquine toxicity in mesothelioma cells. Am J Resp Cell Mol Biol 46(4), 498–506 (2012)

    Article  CAS  Google Scholar 

  55. W. Dai, J.M. Teodoridis, C. Zeller, J. Graham, J. Hersey, J.M. Flanagan, E. Stronach, D.W. Millan, N. Siddiqui, J. Paul, R. Brown, Systematic CpG islands methylation profiling of genes in the wnt pathway in epithelial ovarian cancer identifies biomarkers of progression-free survival. Clin Cancer Res 17(12), 4052–4062 (2011)

    Article  PubMed  CAS  Google Scholar 

  56. J.A. Plumb, G. Strathdee, J. Sludden, S.B. Kaye, R. Brown, Reversal of drug resistance in human tumor xenografts by 2′-deoxy-5-azacytidine-induced demethylation of the hMLH1 gene promoter. Cancer Res 60(21), 6039–6044 (2000)

    PubMed  CAS  Google Scholar 

  57. G. Gifford, J. Paul, P.A. Vasey, S.B. Kaye, R. Brown, The acquisition of hMLH1 methylation in plasma DNA after chemotherapy predicts poor survival for ovarian cancer patients. Clin Cancer Res 10(13), 4420–4426 (2004)

    Article  PubMed  CAS  Google Scholar 

  58. Wu Q, Vasquez KM (2008) Human MLH1 Protein Participates in Genomic Damage Checkpoint Signaling in Response to DNA Interstrand Crosslinks, while MSH2 Functions in DNA Repair. Plos Genet 4 (9)

  59. H.-Y. Su, H.-C. Lai, Y.-W. Lin, C.-Y. Liu, C.-K. Chen, Y.-C. Chou, S.-P. Lin, W.-C. Lin, H.-Y. Lee, M.-H. Yu, Epigenetic silencing of SFRP5 is related to malignant phenotype and chemoresistance of ovarian cancer through Wnt signaling pathway. Int J Cancer 127(3), 555–567 (2010)

    Article  PubMed  CAS  Google Scholar 

  60. J. Staub, J. Chien, Y. Pan, X. Qian, K. Narita, G. Aletti, M. Scheerer, L.R. Roberts, J. Molina, V. Shridhar, Epigenetic silencing of HSulf-1 in ovarian cancer:implications in chemoresistance. Oncogene 26(34), 4969–4978 (2007)

    Article  PubMed  CAS  Google Scholar 

  61. X. Chang, C.L. Monitto, S. Demokan, M.S. Kim, S.S. Chang, X. Zhong, J.A. Califano, D. Sidransky, Identification of hypermethylated genes associated with cisplatin resistance in human cancers. Cancer Res 70(7), 2870–2879 (2010)

    Article  PubMed  CAS  Google Scholar 

  62. W.J. Kim, Q.N. Vo, M. Shrivastav, T.A. Lataxes, K.D. Brown, Aberrant methylation of the ATM promoter correlates with increased radiosensitivity in a human colorectal tumor cell line. Oncogene 21(24), 3864–3871 (2002)

    Article  PubMed  CAS  Google Scholar 

  63. K. Roy, L. Wang, G.M. Makrigiorgos, B.D. Price, Methylation of the ATM promoter in glioma cells alters ionizing radiation sensitivity. Biochem Biophys Res Commun 344(3), 821–826 (2006)

    Article  PubMed  CAS  Google Scholar 

  64. H. De Schutter, H. Geeraerts, E. Verbeken, S. Nuyts, Promoter methylation of TIMP3 and CDH1 predicts better outcome in head and neck squamous cell carcinoma treated by radiotherapy only. Oncol Rep 21(2), 507–513 (2009)

    PubMed  Google Scholar 

  65. S.L. Gerson, Clinical relevance of MGMT in the treatment of cancer. J Clin Oncol 20(9), 2388–2399 (2002)

    Article  PubMed  CAS  Google Scholar 

  66. M.E. Hegi, A.C. Diserens, T. Gorlia, M.F. Hamou, N. de Tribolet, M. Weller, J.M. Kros, J.A. Hainfellner, W. Mason, L. Mariani, J.E. Bromberg, P. Hau, R.O. Mirimanoff, J.G. Cairncross, R.C. Janzer, R. Stupp, MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352(10), 997–1003 (2005)

    Article  PubMed  CAS  Google Scholar 

  67. M. Esteller, J. Garcia-Foncillas, E. Andion, S.N. Goodman, O.F. Hidalgo, V. Vanaclocha, S.B. Baylin, J.G. Herman, Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents. N Engl J Med 343(19), 1350–1354 (2000)

    Article  PubMed  CAS  Google Scholar 

  68. K.H. Huang, S.F. Huang, I.H. Chen, C.T. Liao, H.M. Wang, L.L. Hsieh, Methylation of RASSF1A, RASSF2A, and HIN-1 is associated with poor outcome after radiotherapy, but not surgery, in oral squamous cell carcinoma. Clin Cancer Res 15(12), 4174–4180 (2009)

    Article  PubMed  CAS  Google Scholar 

  69. Q.Z. Zhao, K.F. Dou, Methylation of Ras association domain family protein 1, isoform A correlated with proliferation and drug resistance in hepatocellular carcinoma cell line SMMC-7721. J Gastroenterol Hepatol 22(5), 683–689 (2007)

    PubMed  CAS  Google Scholar 

  70. S. Honda, M. Haruta, W. Sugawara, F. Sasaki, M. Ohira, T. Matsunaga, H. Yamaoka, H. Horie, N. Ohnuma, A. Nakagawara, E. Hiyama, S. Todo, Y. Kaneko, The methylation status of RASSF1A promoter predicts responsiveness to chemotherapy and eventual cure in hepatoblastoma patients. Int J Cancer 123(5), 1117–1125 (2008)

    Article  PubMed  CAS  Google Scholar 

  71. J. Bernier, E.J. Hall, A. Giaccia, Radiation oncology: a century of achievements. Nat Rev Cancer 4(9), 737–747 (2004)

    Article  PubMed  CAS  Google Scholar 

  72. D. Wang, S.J. Lippard, Cellular processing of platinum anticancer drugs. Nat Rev Drug Discov 4(4), 307–320 (2005)

    Article  PubMed  CAS  Google Scholar 

  73. M.B. Kastan, J. Bartek, Cell-cycle checkpoints and cancer. Nature 432(7015), 316–323 (2004)

    Article  PubMed  CAS  Google Scholar 

  74. Y. Shiloh, ATM and related protein kinases: safeguarding genome integrity. Nat Rev Cancer 3(3), 155–168 (2003)

    Article  PubMed  CAS  Google Scholar 

  75. F. Roossink, H.W. Wieringa, M.G. Noordhuis, K.A. Ten Hoor, M. Kok, L. Slagter-Menkema, G.H. de Bock, H. Hollema, E. Pras, E.G.E. de Vries, S. de Jong, A.G.J. van der Zee, E. Schuuring, G.B.A. Wisman, M.A.T.M. van Vugt, The Role of ATM and 53BP1 as Predictive Markers and Therapeutic Targets in Cervical Cancer. Int J Cancer (2012). doi:10.1002/ijc.27488

  76. J.P.T. Morris, S.C. Wang, M. Hebrok, KRAS, Hedgehog, Wnt and the twisted developmental biology of pancreatic ductal adenocarcinoma. Nat Rev Cancer 10(10), 683–695 (2010)

    Article  PubMed  CAS  Google Scholar 

  77. S. Angers, R.T. Moon, Proximal events in Wnt signal transduction. Nat Rev Mol Cell Biol 10(7), 468–477 (2009)

    PubMed  CAS  Google Scholar 

  78. Y. Kawano, R. Kypta, Secreted antagonists of the Wnt signalling pathway. J Cell Sci 116(13), 2627–2634 (2003)

    Article  PubMed  CAS  Google Scholar 

  79. Y.W. Lin, M.T. Chung, H.C. Lai, M. De Yan, Y.L. Shih, C.C. Chang, M.H. Yu, Methylation analysis of SFRP genes family in cervical adenocarcinoma. J Cancer Res Clin Oncol 135(12), 1665–1674 (2009)

    Article  PubMed  CAS  Google Scholar 

  80. J. Ko, K.S. Ryu, Y.H. Lee, D.S. Na, Y.S. Kim, Y.M. Oh, I.S. Kim, J.W. Kim, Human Secreted Frizzled-Related Protein Is Down-regulated and Induces Apoptosis in Human Cervical Cancer. Exp Cell Res 280(2), 280–287 (2002)

    Article  PubMed  CAS  Google Scholar 

  81. E.F. Wagner, A.R. Nebreda, Signal integration by JNK and p38 MAPK pathways in cancer development. Nat Rev Cancer 9(8), 537–549 (2009)

    Article  PubMed  CAS  Google Scholar 

  82. J.S. Sebolt-Leopold, R. Herrera, Targeting the mitogen-activated protein kinase cascade to treat cancer. Nat Rev Cancer 4(12), 937–947 (2004)

    Article  PubMed  CAS  Google Scholar 

  83. A.E. Karnoub, R.A. Weinberg, Ras oncogenes: split personalities. Nat Rev Mol Cell Biol 9(7), 517–531 (2008)

    Article  PubMed  CAS  Google Scholar 

  84. M.G. Noordhuis, J.J.H. Eijsink, K.A. ten Hoor, F. Roossink, H. Hollema, H.J.G. Arts, E. Pras, J.H. Maduro, A.K.L. Reyners, G.H. de Bock, G.B.A. Wisman, E. Schuuring, A.G.J. van der Zee, Expression of Epidermal Growth Factor Receptor (EGFR) and Activated EGFR Predict Poor Response to (Chemo)radiation and Survival in Cervical Cancer. Clin Cancer Res 15(23), 7389–7397 (2009)

    Article  PubMed  CAS  Google Scholar 

  85. Y. Liu, B. Cui, Y. Qiao, Y. Zhang, Y. Tian, J. Jiang, D. Ma, B. Kong, Phosphoinositide-3-kinase inhibition enhances radiosensitization of cervical cancer in vivo. Int J Gynecol Cancer 21(1), 100–105 (2011)

    Article  PubMed  CAS  Google Scholar 

  86. D.D. Meira, V.H. de Almeida, J.S. Mororo, I. Nobrega, L. Bardella, R.L. Silva, R.M. Albano, C.G. Ferreira, Combination of cetuximab with chemoradiation, trastuzumab or MAPK inhibitors: mechanisms of sensitisation of cervical cancer cells. Br J Cancer 101(5), 782–791 (2009)

    Article  PubMed  CAS  Google Scholar 

  87. M. Ongenaert, G.B. Wisman, H.H. Volders, A.J. Koning, A.G. Zee, W. van Criekinge, E. Schuuring, Discovery of DNA methylation markers in cervical cancer using relaxation ranking. BMC Med Genomics 1, 57 (2008). doi:10.1186/1755-8794-1-57

    Article  PubMed  Google Scholar 

  88. M.O. Hoque, M.S. Kim, K.L. Ostrow, J. Liu, G.B. Wisman, H.L. Park, M.L. Poeta, C. Jeronimo, R. Henrique, A. Lendvai, E. Schuuring, S. Begum, E. Rosenbaum, M. Ongenaert, K. Yamashita, J. Califano, W. Westra, A.G. van der Zee, W. Van Criekinge, D. Sidransky, Genome-wide promoter analysis uncovers portions of the cancer methylome. Cancer Res 68(8), 2661–2670 (2008)

    Article  PubMed  CAS  Google Scholar 

  89. J.J. Eijsink, A. Lendvai, V. Deregowski, H.G. Klip, G. Verpooten, L. Dehaspe, G.H. de Bock, H. Hollema, W. van Criekinge, E. Schuuring, A.G. van der Zee, G.B. Wisman, A four gene methylation marker panel as triage test in hr-HPV positive patients. Int J Cancer 130(8), 1861–1869 (2012)

    Article  PubMed  CAS  Google Scholar 

  90. E.R. Nijhuis, N. Reesink-Peters, G.B. Wisman, H.W. Nijman, J. van Zanden, H. Volders, H. Hollema, A.J. Suurmeijer, E. Schuuring, A.G. van der Zee, An overview of innovative techniques to improve cervical cancer screening. Cell Oncol 28(5–6), 233–246 (2006)

    PubMed  Google Scholar 

  91. D. Serre, B.H. Lee, A.H. Ting, MBD-isolated Genome Sequencing provides a high-throughput and comprehensive survey of DNA methylation in the human genome. Nucleic Acids Res 38(2), 391–399 (2010)

    Article  PubMed  CAS  Google Scholar 

  92. S. Stolzenburg, A. Bilsland, W.N. Keith, M.G. Rots, Modulation of gene expression using zinc finger-based artificial transcription factors. Methods Mol Biol 649, 117–132 (2010)

    Article  PubMed  CAS  Google Scholar 

  93. S. Koul, J. Houldsworth, M.M. Mansukhani, A. Donadio, J.M. McKiernan, V.E. Reuter, G.J. Bosl, R.S. Chaganti, V.V. Murty, Characteristic promoter hypermethylation signatures in male germ cell tumors. Mol Cancer 1, 8 (2002)

    Article  PubMed  Google Scholar 

  94. S.L. Lim, P. Smith, N. Syed, C. Coens, H. Wong, M. van der Burg, P. Szlosarek, T. Crook, J.A. Green, Promoter hypermethylation of FANCF and outcome in advanced ovarian cancer. Br J Cancer 98(8), 1452–1456 (2008)

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by a grant from the Dutch Cancer Society (RUG 2007–3719).

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Author information

Authors and Affiliations

  1. Department of Gynecologic Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

    Frank Roossink, G. Bea A. Wisman & Ate G. J. van der Zee

  2. Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

    Steven de Jong

  3. Department of Pathology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

    Ed Schuuring

  4. Department of Pathology and Medical Biology (EA10), University Medical Center Groningen, P.O. Box 30001, NL-9700, RB, Groningen, The Netherlands

    Ed Schuuring

Authors
  1. Frank Roossink
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Steven de Jong
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G. Bea A. Wisman
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ate G. J. van der Zee
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ed Schuuring
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ed Schuuring.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Roossink, F., de Jong, S., Wisman, G.B.A. et al. DNA hypermethylation biomarkers to predict response to cisplatin treatment, radiotherapy or chemoradiation: the present state of art. Cell Oncol. 35, 231–241 (2012). https://doi.org/10.1007/s13402-012-0091-7

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13402-012-0091-7

Keywords

Search

Navigation