Epigenetic events underlie the pathogenesis of sinonasal papillomas

Abstract

Benign inverted papillomas have been reported as monoclonal but lacking common genetic alterations identified in squamous cell carcinoma of the head and neck. Epigenetic changes alter the heritable state of gene expression and chromatin organization without change in DNA sequence. We investigated whether epigenetic events of aberrant promoter hypermethylation in genes known to be involved in squamous head and neck cancer underlie the pathogenesis of sinonasal papillomas. Ten formalin-fixed paraffin DNA samples from three inverted papilloma cases, two exophytic (everted) papilloma cases, and two cases with inverted and exophytic components were studied. DNA was obtained from microdissected areas of normal and papilloma areas and examined using a panel of 41 gene probes, designed to interrogate 35 unique genes for aberrant methylation status (22 genes) using the methylation-specific multiplex-ligation-specific polymerase assay. Methylationspecific PCR was employed to confirm aberrant methylation detected by the methylation-specific multiplexligation-specific polymerase assay. All seven cases indicated at least one epigenetic event of aberrant promoter hypermethylation. The CDKN2B gene was a consistent target of aberrant methylation in six of seven cases. Methylation-specific PCR confirmed hypermethylation of CDKN2B. Recurrent biopsies from two inverted papilloma cases had common epigenetic events. Promoter hypermethylation of CDKN2B was a consistent epigenetic event. Common epigenetic alterations in recurrent biopsies underscore a monoclonal origin for these lesions. Epigenetic events contribute to the underlying pathogenesis of benign inverted and exophytic papillomas. As a consistent target of aberrant promoter hypermethylation, CDKN2B may serve as an important epigenetic biomarker for gene reactivation studies.

Elevated expression of USP22 in correlation with poor prognosis in patients with invasive breast cancer

“…Histone modifications are not only to play a role in tumorigenesis but also to be used for cancer diagnosis and follow-up of treatments (Bolden et al 2006;Stephen et al 2007). Ubiquitination, one of the histone modifications in the tail region of histones, is involved in transcription, DNA damage repair, and meiosis (Giannattasio et al 2005;Zhang et al 2005).…”

Strategic Approach to Validating Methylated Genes as Biomarkers for Breast Cancer

“…It seems possible that combining DNA methylation markers and cytology might increase sensitivity without decreasing specificity in diagnosis. Significant differences in DNA methylation signatures between certain benign breast conditions, such as papilloma and DCIS, compared with cancer have been shown (31,32). Promoter hypermethylation of RUNX3 was significantly higher in the neoplastic breast samples than in normal breast tissues (29).…”

“…This approach has identified several methylation markers that have potential to improve cancer diagnosis, risk assessment, and treatment (Table 2; refs. [23][24][25][26][27][28][29][30][31][32][33]. Several genes, including RASSF1a, HIn1, Cyclin D2, have shown consistent association with breast cancer in several independent studies, although the magnitudes of these genes' methylation are variable.…”

Epigenetics in Head and Neck Squamous Cell Carcinoma

“…Stephen et al (2007) investigated whether epigenetic events of aberrant promoter hypermethylation in genes known to be involved in squamous head and neck cancer underlie the pathogenesis of sinonasal papillomas. Ten formalin-fixed paraffin DNA samples from three inverted papilloma cases, two exophytic (everted) papilloma cases, and two cases with inverted and exophytic components were studied.…”

“…Epigenetic events contribute to the underlying pathogenesis of benign inverted and exophytic papillomas. As a consistent target of aberrant promoter hypermethylation, CDKN2B may serve as an important epigenetic biomarker for gene reactivation studies (Stephen et al, 2007).…”