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VOLUME 1 , ISSUE 2 ( May-August, 2010 ) > List of Articles

RESEARCH ARTICLE

Consistent DNA Hypermethylation Patterns in Laryngeal Papillomas

Josena K Stephen, Kang Mei Chen, Veena Shah, Vanessa G Schweitzer, Glendon Gardner, Michael S Benninger, Maria J Worsham

Citation Information : Stephen JK, Chen KM, Shah V, Schweitzer VG, Gardner G, Benninger MS, Worsham MJ. Consistent DNA Hypermethylation Patterns in Laryngeal Papillomas. Int J Head Neck Surg 2010; 1 (2):69-77.

DOI: 10.5005/jp-journals-10001-1013

Published Online: 01-12-2011

Copyright Statement:  Copyright © 2010; The Author(s).


Abstract

Introduction

This study examined the contribution of promoter hypermethylation to the pathogenesis of respiratory papillomatosis (RP), including recurrences (RRP) and progression to squamous cell carcinoma (SSC).

Materials and methods

A retrospective cohort of 25 laryngeal papilloma cases included 21 RRP, two of which progressed to SCC. Aberrant methylation status was determined using the multigene (22 tumor suppressor genes) methylation-specific multiplex ligationdependent probe amplification assay and confirmed using methylation specific PCR.

Results

Twenty genes had altered DNA methylation in 22 of 25 cases. Aberrant methylation of CDKN2B and TIMP3 was most frequent. Promoter hypermethylation of BRCA2, APC, CDKN2A and CDKN2B was detected in 2 RRP cases with subsequent progression to SCC. Of the 25 cases, 22 were positive for HPV-6, 2 for HPV-11 and 1 for HPV-16 and 33.

Conclusion

Consistent aberrant methylation of multiple tumor suppressor genes contributes to the pathogenesis of laryngeal papillomas. Persistent aberrant DNA methylation events in 2 RRP cases that progressed to cancer indicate an epigenetic monoclonal progression continuum to SCC.

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