An Epigenetically Derived Monoclonal Origin for Recurrent Respiratory Papillomatosis

Abstract

To investigate the contribution of promoter methylation-mediated epigenetic events in recurrent respiratory papillomatosis tumorigenesis. Design: Archival tissue DNA, extracted from microdissected papilloma lesions, was interrogated for methylation status by means of the novel, multigene methylationspecific multiplex ligation-dependent probe amplification assay. Subjects: Fifteen subjects with recurrent respiratory papillomatosis, 3 females and 12 males, all with adult onset of illness (age range, 23-73 years) except for 1 female patient with juvenile onset (1 year old). Results: Promoter hypermethylation was recorded in 14 of 15 cases, and 19 of 22 unique methylation-prone can

Consistent DNA Hypermethylation Patterns in Laryngeal Papillomas

“…The high frequency of DNA hypermethylation events in this study supports the utilization of gene silencing mechanisms as one of the driving forces behind the growth of laryngeal papillomas, reiterating DNA hypermethylation events as hallmarks of RP pathogenesis, some of which are initiating clonal alterations in the recurrence continuum in some RRP cases 14. Aberrant methylation of BRCA2, APC , CDKN2A and CDKN2B , confirmed by MSP and detected in the initial and all subsequent transformation biopsies in RRP Cases 1 and 5, appears to be an early event in the pathogenesis of laryngeal papillomatosis tracing a monoclonal progression continuum to SCC.…”

“…Identical abnormally methylated genes were found in recurrent biopsies of 5 of 15 RRP cases and an aberrantly methylated CDKN2B gene linked all 5 cases (cases 4, 7, 11, 12, 13) 14. MSP confirmed aberrant methylation of CDKN2B in RRP cases 4, 7, 11 and 12 in multiple recurrent biopsies (MSP for Case 13 was not performed).…”

Translational Research Techniques for the Facial Plastic Surgeon: An Overview

“…[57][58][59][60][61][62] However, the hypomethylated profile seen in the study directly contrasts the hypermethylation profile commonly seen in many malignancies; rather similarities can be seen between keloids and benign tumors. 57,58 Indeed, a pathway analysis conducted of the genes involved in hypomethylation revealed that many genes were associated with tumorlike pathways. 63 Additionally, it was shown that much of the DNA hypermethylation that did occur was in nonpromoter regions.…”

Novel approaches to global mining of aberrantly methylated promoter sites in squamous head and neck cancer

“…The whole-genome methylation approach indicated 231 potential new genes with hypermethylated promoter regions not previously reported in HNSCC and highlights the limita-tions of our previous candidate multi-gene approach. 12,18,21,22 These studies, employing larger HNSCC study cohorts, identified a mere handful of genes when compared to the global methylation strategy in this report. However, a limitation of this study remains the small number of patient samples and lack of control tissue.…”