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Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer

Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer

Published on: September 18, 2020

Consistent DNA hypermethylation patterns in laryngeal papillomas.

Josena K Stephen¹, Kang Mei Chen, Veena Shah

¹Department of Otolaryngology-Head and Neck Surgery and Research Division, Henry Ford Hospital, Detroit, MI 48202.

International Journal of Head and Neck Surgery

|May 24, 2011

Summary

Aberrant DNA methylation in tumor suppressor genes contributes to respiratory papillomatosis (RP) and its progression to squamous cell carcinoma (SCC). Persistent methylation changes were observed in RRP cases that developed SCC, suggesting epigenetic changes drive cancer development.

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Published on: March 11, 2014

Area of Science:

Oncology
Epigenetics
Otolaryngology

Background:

Respiratory papillomatosis (RP) is a laryngeal condition often caused by HPV.
Understanding the epigenetic mechanisms, such as DNA methylation, is crucial for RP pathogenesis and malignant transformation.
Recurrent respiratory papillomatosis (RRP) can progress to squamous cell carcinoma (SCC).

Purpose of the Study:

To investigate the role of promoter hypermethylation in tumor suppressor genes in the pathogenesis of RP, RRP, and progression to SCC.
To identify specific genes and methylation patterns associated with RP development and malignant changes.

Main Methods:

Retrospective analysis of 25 laryngeal papilloma cases, including RRP and SCC.
Utilized methylation-specific multiplex ligation-dependent probe amplification assay for multi-gene methylation analysis (22 tumor suppressor genes).
Confirmed aberrant methylation using methylation-specific PCR and identified HPV genotypes.

Main Results:

Twenty genes showed altered DNA methylation in 22 out of 25 cases.
CDKN2B and TIMP3 promoter hypermethylation were most frequent.
BRCA2, APC, CDKN2A, and CDKN2B hypermethylation were detected in 2 RRP cases that progressed to SCC. HPV-6 was the most prevalent genotype.

Conclusions:

Aberrant methylation of multiple tumor suppressor genes is a significant factor in laryngeal papilloma pathogenesis.
Persistent aberrant DNA methylation in RRP cases progressing to SCC suggests an epigenetic continuum towards malignancy.
These findings highlight the importance of epigenetic alterations in the natural history of RP.