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BRCA1 promoter methylation is a marker of better response to platinum–taxane-based therapy in sporadic epithelial ovarian cancer

  • Original Article – Cancer Research
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Abstract

Background

The aim of the current study was to investigate the role of BRCA1 promoter methylation as predictive factor of response to platinum–taxane-based therapy in sporadic ovarian cancer.

Patients and methods

BRCA1 promoter methylation was analyzed in 42 sporadic epithelial ovarian cancers. The results were validated in a second cohort of 137 ovarian cancer patients.

Results

BRCA1 promoter methylation was observed in 35.7 % of patients in the first group and in 33.6 % in the second group. BRCA1 promoter methylation was associated with significant increase in median progression-free survival (PFS) of ovarian cancer patients receiving adjuvant platinum–taxane-based chemotherapy (P = 0.008). Multivariate analysis revealed that BRCA1 promoter methylation remains a favorable factor in regard to PFS (HR 0.52; 95 % CI 0.32–0.85, P = 0.009) after adjustment for other prognostic factors. Under the patients with recurrent disease, BRCA1 promoter methylation was associated with significant longer median PFS of 18.5 months in comparison with 12.8 months PFS for patients without BRCA1 promoter methylation.

Conclusions

BRCA1 promoter methylation is predictive for better response to platinum–taxane-based therapy in EOC.

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References

  • Boyd J, Sonoda Y, Federici MG, Bogomolniy F, Rhei E, Maresco DL, Saigo PE, Almadrones LA, Barakat RR, Brown CL, Chi DS, Curtin JP, Poynor EA, Hoskins WJ (2000) Clinicopathologic features of BRCA-linked and sporadic ovarian cancer. JAMA 17:2260–2265

    Article  Google Scholar 

  • Buller RE, Shahin MS, Geisler JP, Zogg M, De Young BR, Davis CS (2002) Failure of BRCA1 dysfunction to alter ovarian cancer survival. Clin Cancer Res 5:1196–1202

    Google Scholar 

  • Carser JE, Quinn JE, Michie CO, O’Brien EJ, McCluggage WG, Maxwell P, Lamers E, Lioe TF, Williams AR, Kennedy RD, Gourley C, Harkin DP (2011) BRCA1 is both a prognostic and predictive biomarker of response to chemotherapy in sporadic epithelial ovarian cancer. Gynecol Oncol 3:492–498

    Article  Google Scholar 

  • Catteau A, Morris JR (2002) BRCA1 methylation: a significant role in tumour development? Semin Cancer Biol 12(5):359–371

    Article  CAS  PubMed  Google Scholar 

  • Chaudhry P, Srinivasan R, Patel FD (2009) Utility of gene promoter methylation in prediction of response to platinum-based chemotherapy in epithelial ovarian cancer (EOC). Cancer Investig 8:877–884

    Article  Google Scholar 

  • Chetrit A, Hirsh-Yechezkel G, Ben David Y, Lubin F, Friedman E, Sadetzki S (2008) Effect of BRCA1/2 mutations on long-term survival of patients with invasive ovarian cancer: the national Israeli study of ovarian cancer. J Clin Oncol 1:20–25

    Article  Google Scholar 

  • Guendel I, Carpio L, Pedati C, Schwartz A, Teal C, Kashanchi F, Kehn-Hall K (2010) Methylation of the tumor suppressor protein, BRCA1, influences its transcriptional cofactor function. PLoS One 6:e11379

    Article  Google Scholar 

  • Harter P, Hilpert F, Mahner S, Heitz F, Pfisterer J, du BA (2010) Systemic therapy in recurrent ovarian cancer: current treatment options and new drugs. Expert Rev Anticancer Ther 1:81–88

    Article  Google Scholar 

  • Ignatov T, Poehlmann A, Ignatov A, Schinlauer A, Costa SD, Roessner A, Kalinski T, Bischoff J (2013) BRCA1 promoter methylation is a marker of better response to anthracycline-based therapy in sporadic TNBC. Breast Cancer Res Treat 2:205–212

    Article  Google Scholar 

  • Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ (2009) Cancer statistics, 2009. CA Cancer J Clin 4:225–249

    Article  Google Scholar 

  • Knudson AG Jr (1971) Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci USA 4:820–823

    Article  Google Scholar 

  • Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S, Liu Q, Cochran C, Bennett LM, Ding W (1994) A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 5182:66–71

    Article  Google Scholar 

  • Quinn JE, Carser JE, James CR, Kennedy RD, Harkin DP (2009) BRCA1 and implications for response to chemotherapy in ovarian cancer. Gynecol Oncol 1:134–142

    Article  Google Scholar 

  • Senturk E, Cohen S, Dottino PR, Martignetti JA (2010) A critical re-appraisal of BRCA1 methylation studies in ovarian cancer. Gynecol Oncol 2:376–383

    Article  Google Scholar 

  • Sherr CJ (2004) Principles of tumor suppression. Cell 2:235–246

    Article  Google Scholar 

  • Shilpa V, Bhagat R, Premalata CS, Pallavi VR, Ramesh G, Krishnamoorthy L (2014) BRCA1 promoter hypermethylation and protein expression in ovarian carcinoma-an Indian study. Tumour Biol 35:4277–4284

    Article  CAS  PubMed  Google Scholar 

  • Stefansson OA, Villanueva A, Vidal A, Marti L, Esteller M (2012) BRCA1 epigenetic inactivation predicts sensitivity to platinum-based chemotherapy in breast and ovarian cancer. Epigenetics 11:1225–1229

    Article  Google Scholar 

  • Suijkerbuijk KP, Fackler MJ, Sukumar S, van Gils CH, van Laar T, Van der WE, Vooijs M, van Diest PJ (2008) Methylation is less abundant in BRCA1-associated compared with sporadic breast cancer. Ann Oncol 11:1870–1874

    Article  Google Scholar 

  • Swisher EM, Gonzalez RM, Taniguchi T, Garcia RL, Walsh T, Goff BA, Welcsh P (2009) Methylation and protein expression of DNA repair genes: association with chemotherapy exposure and survival in sporadic ovarian and peritoneal carcinomas. Mol Cancer 8:48

    Article  PubMed Central  PubMed  Google Scholar 

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

    Article  Google Scholar 

  • Turner N, Tutt A, Ashworth A (2004) Hallmarks of ‘BRCAness’ in sporadic cancers. Nat Rev Cancer 10:814–819

    Article  Google Scholar 

  • Vencken PM, Kriege M, Hoogwerf D, Beugelink S, van der Burg ME, Hooning MJ, Berns EM, Jager A, Collee M, Burger CW, Seynaeve C (2011) Chemosensitivity and outcome of B. Ann Oncol 6:1346–1352

    Article  Google Scholar 

  • Weberpals JI, Tu D, Squire JA, Amin MS, Islam S, Pelletier LB, O’Brien AM, Hoskins PJ, Eisenhauer EA (2011) Breast cancer 1 (BRCA1) protein expression as a prognostic marker in sporadic epithelial ovarian carcinoma: an NCIC CTG OV.16 correlative study. Ann Oncol 11:2403–2410

    Article  Google Scholar 

  • Yang D, Khan S, Sun Y, Hess K, Shmulevich I, Sood AK, Zhang W (2011) Association of BRCA1 and BRCA2 mutations with survival, chemotherapy sensitivity, and gene mutator phenotype in patients with ovarian cancer. JAMA 14:1557–1565

    Article  Google Scholar 

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Conflict of interest

We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Otto-von-Guericke University, Magdeburg, Germany

    T. Ignatov, H. Eggemann, S. D. Costa & A. Ignatov

  2. Department of Pathology, Otto-von-Guericke University, Magdeburg, Germany

    A. Roessner & T. Kalinski

Authors
  1. T. Ignatov
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  2. H. Eggemann
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  3. S. D. Costa
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  4. A. Roessner
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  5. T. Kalinski
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  6. A. Ignatov
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Correspondence to A. Ignatov.

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Ignatov, T., Eggemann, H., Costa, S.D. et al. BRCA1 promoter methylation is a marker of better response to platinum–taxane-based therapy in sporadic epithelial ovarian cancer. J Cancer Res Clin Oncol 140, 1457–1463 (2014). https://doi.org/10.1007/s00432-014-1704-5

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  • DOI: https://doi.org/10.1007/s00432-014-1704-5

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