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Prognostic significance of epigenetic inactivation of p16, p15, MGMT and DAPK genes in follicular lymphoma

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Abstract

In this study, methylation-specific polymerase chain reaction was used to investigate the role and potential prognostic significance of the methylation status of p16, p15, MGMT and DAPK genes in 32 specimens of follicular lymphoma (FL). Hypermethylation of p15 gene was associated with lower hemoglobin level (P = 0.020) and MGMT/DAPK comethylation with relapsed disease (P = 0.018). Among all patients with FL, there was no significant difference in the overall survival between those with hypermethylated and unmethylated of any examined genes. Therefore, we analyzed methylation in the different groups according to FL International Prognostic Index (FLIPI) and tumor grade. In the high-risk group, patients with hypermethylated p16 gene had significant lower overall survival than those with unmethylated p16 (P = 0.006) and trend toward shorter failure-free survival (P = 0.068). In the same risk group, there was a trend toward longer overall survival for patients with hypermethylated MGMT gene, compared to those with unmethylated MGMT gene (P = 0.066). p15 methylation had impact on shorter overall survival in grade I group of patients (P = 0.013), and DAPK methylation tended to have impact on shorter failure-free survival in the whole examined group (P = 0.079). Our results suggest that promoter methylation of p16 and MGMT genes could have prognostic value when used in combination with the FLIPI and p15 methylation in combination with tumor grade. Concurrent methylation of MGMT and DAPK genes could be the marker of tumor chemoresistance and disease recurrence.

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Acknowledgments

This work was supported by the Grant 173049 from the Ministry of Education, Science and Technological Development of the Republic of Serbia.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Institute of Nuclear Sciences “Vinča”, University of Belgrade, 11001, Belgrade, Serbia

    Milena Krajnović, Radoslav Davidović, Bogomir Dimitrijević & Koviljka Krtolica

  2. Medical Faculty, University of Belgrade, 11000, Belgrade, Serbia

    Milica Radojković

  3. Clinical Center Dr. Dragisa Misovic, 11000, Belgrade, Serbia

    Milica Radojković

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  1. Milena Krajnović
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  2. Milica Radojković
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Correspondence to Milena Krajnović.

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Krajnović, M., Radojković, M., Davidović, R. et al. Prognostic significance of epigenetic inactivation of p16, p15, MGMT and DAPK genes in follicular lymphoma. Med Oncol 30, 441 (2013). https://doi.org/10.1007/s12032-012-0441-3

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