Consistent DNA Hypermethylation Patterns in Laryngeal Papillomas

JOURNAL TITLE: International Journal of Head and Neck Surgery

Author
1. Glendon Gardner
2. Michael S Benninger
3. Maria J Worsham
4. Josena K Stephen
5. Kang Mei Chen
6. Veena Shah
7. Vanessa G Schweitzer
ISSN
0975-7899
DOI
10.5005/jp-journals-10001-1013
Volume
1
Issue
2
Publishing Year
2010
Pages
9
Author Affiliations
    1. Department of Otolaryngology, Head and Neck Surgery and Research Division, Henry Ford Hospital, Detroit, MI 48202, USA
    1. Department of Otolaryngology, Head and Neck Surgery and Research Division, Henry Ford Hospital, Detroit, MI 48202, USA
    1. Department of Pathology, Henry Ford Hospital, Detroit, MI 48202, USA
    1. Department of Otolaryngology, Head and Neck Surgery and Research Division, Henry Ford Hospital, Detroit, MI 48202, USA
    1. Department of Otolaryngology, Head and Neck Surgery and Research Division, Henry Ford Hospital, Detroit, MI 48202, USA
    1. Head and Neck Institute, Cleveland Clinic, Cleveland, OH 44195, USA
    1. Department of Otolaryngology, Head and Neck Surgery and Research Division, Henry Ford Hospital, Detroit, MI 48202, USA
  • Article keywords

    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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