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Promoter hypermethylation in tumour suppressor genes and response to interleukin-2 treatment in bladder cancer: a pilot study

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Abstract

Purpose

Non-muscle invasive bladder cancer (BC) is a highly recurrent disease, with the first recurrences arising shortly after transurethral resection of the bladder (TURB). Topical administration of interleukin-2 (IL-2) has been shown as an effective adjuvant therapy for BC; however, predictive biomarkers that may identify suitable subgroups of patients are lacking. In this pilot study we sought to determine the prognostic value of epigenetic and genetic inactivation of tumour suppressor genes (TSGs) among BC patients treated with IL-2.

Methods

After complete TURB, patients with multifocal superficial BC were treated with five daily intravesical instillations of IL-2. Promoter hypermethylation in six TSGs and the TP53 gene mutations were prospectively assessed by methylation-specific PCR and automated capillary single-strand conformation polymorphism in 21 primary bladder cancer specimens and ten bladder wall biopsies collected during follow-up.

Results

After IL-2 treatment, 9 out of 21 (43%) patients did not develop recurrent tumour within the 1 year of follow-up period. The mean duration of recurrence-free survival in the rest of the study group was 112 days. In the current pilot study, BC with p16 gene hypermethylation had a lower risk of recurrence after treatment with IL-2, as compared to IL-2 treated BC without p16 hypermethylation (p = 0.02). Significant associations were observed between tumour grade and the mean methylation index (p = 0.003), as well as the hypermethylation of the RARβ gene (p = 0.048).

Conclusion

Our preliminary data suggest that DNA methylation biomarkers may assist in selection of BC patients for efficient IL-2 therapy.

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Acknowledgments

This work was supported by grants B-17/2005 and C-03/2007 from the Lithuanian State Science and Studies Foundation, and COST grant BM0703. We thank Dr. D. Characiejus for organizing IL-2 treatment at the Oncology Institute of Vilnius University and for valuable comments on the manuscript.

Conflict of interest statement

We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Faculty of Natural Sciences, Vilnius University, Ciurlionio 21, 3101, Vilnius, Lithuania

    Sonata Jarmalaite, Rasa Andrekute & Asta Scesnaite

  2. Institute of Oncology, Vilnius University, Vilnius, Lithuania

    Kestutis Suziedelis

  3. Biological Mechanisms and Prevention of Work-Related Diseases, Finnish Institute of Occupational Health, Helsinki, Finland

    Kirsti Husgafvel-Pursiainen

  4. Faculty of Medicine, Vilnius University, Vilnius, Lithuania

    Feliksas Jankevicius

Authors
  1. Sonata Jarmalaite
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  2. Rasa Andrekute
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  3. Asta Scesnaite
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  4. Kestutis Suziedelis
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  5. Kirsti Husgafvel-Pursiainen
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  6. Feliksas Jankevicius
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Correspondence to Sonata Jarmalaite.

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Jarmalaite, S., Andrekute, R., Scesnaite, A. et al. Promoter hypermethylation in tumour suppressor genes and response to interleukin-2 treatment in bladder cancer: a pilot study. J Cancer Res Clin Oncol 136, 847–854 (2010). https://doi.org/10.1007/s00432-009-0725-y

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  • DOI: https://doi.org/10.1007/s00432-009-0725-y

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