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Frequency of Genetic and Epigenetic Alterations of p14ARF and p16INK4A in Head and Neck Cancer in a Hungarian Population

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Pathology & Oncology Research

Abstract

Occurrence of genetic and epigenetic alterations affecting p14ARF and p16INK4A were investigated in tumour samples of 37 oral (OSCC) and 28 laryngeal squamous cell cancer (LSCC) patients, and compared to exfoliated buccal epithelial cells of 68 healthy controls. Presence of deletions and mutations/polymorphisms affecting exons were examined using sequencing. Methylation status of promoters was assessed by methylation-specific PCR. Chi-square and Fisher’s exact tests were used to compare frequency of events. Exon deletions were found in four controls, one OSCC and 22 LSCC patients; the latter significantly differed from controls (p < 0.001). Only two mutations (T24610A and C24702A) were in p16 exon 1 of two OSCC patients. Polymorphisms G28575A (Ala140Thr), G31292C (C540G) and G28608A were found in both patient groups. The p14 promoter was unmethylated in 86.7 % of OSCC and in 85.7 % of LSCC patients; for the p16 promoter these rates were 69.0 % and 76.2 % for OSCC and LSCC patients, respectively. Combining the two patient groups, unmethylated promoter was significantly less frequent in case of both p14 and p16 (p = 0.043 and p = 0.001, respectively) compared to the control group. In summary, exon deletion may be important in LSCC, while promoter methylation was relatively frequent in both patient groups.

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Acknowledgements

The work was supported by National Scientific Research Fund (OTKA) F046749, Mecenatura Mec-13/2011 and TÁMOP-4.2.2/B-10/1-2010-0024 grants. The TÁMOP project is co-financed by the European Union and the European Social Fund. The funding sources had no role in study design, data collection and interpretation or writing of the manuscript.

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Authors and Affiliations

  1. Department of Medical Microbiology, Faculty of Medicine, University of Debrecen, H-4032, Debrecen, Nagyerdei krt. 98, Hungary

    Andrea Kis, Tímea Zsófia Tatár, Tamás Gáll, Tamás Major, Lajos Gergely & Krisztina Szarka

  2. Department of Dentoalveolar and Maxillofacial Surgery, Faculty of Medicine, University of Debrecen, H-4032, Debrecen, Nagyerdei krt. 98, Hungary

    Róbert Boda & Pál Redl

  3. Department of Periodontology, Faculty of Medicine, University of Debrecen, H-4032, Debrecen, Nagyerdei krt. 98, Hungary

    Ildikó Tar

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  1. Andrea Kis
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Correspondence to Krisztina Szarka.

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Kis, A., Tatár, T.Z., Gáll, T. et al. Frequency of Genetic and Epigenetic Alterations of p14ARF and p16INK4A in Head and Neck Cancer in a Hungarian Population. Pathol. Oncol. Res. 20, 923–929 (2014). https://doi.org/10.1007/s12253-014-9775-9

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