OBJECTIVE: 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 methylation-specific 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 cancer genes in the multigene panel had altered DNA methylation in at least 1 laryngeal papilloma biopsy specimen. Identical abnormally methylated genes were found in 5 of 15 recurrent cases, of which the CDKN2B gene was hypermethylated in all 5 cases. Dissimilar epigenetic events were noted in the remaining cases. CONCLUSIONS: A clonal origin was derived for 5 of 15 recurrent respiratory papillomatosis biopsy specimens based on identical epigenetic events. The high frequency of epigenetic events, characterized by consistent promoter hypermethylation of multiple tumor suppressor genes, points to the use of gene silencing mechanisms in the pathogenesis of recurrent respiratory papillomatosis.
OBJECTIVE: 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 methylation-specific 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 cancer genes in the multigene panel had altered DNA methylation in at least 1 laryngeal papilloma biopsy specimen. Identical abnormally methylated genes were found in 5 of 15 recurrent cases, of which the CDKN2B gene was hypermethylated in all 5 cases. Dissimilar epigenetic events were noted in the remaining cases. CONCLUSIONS: A clonal origin was derived for 5 of 15 recurrent respiratory papillomatosis biopsy specimens based on identical epigenetic events. The high frequency of epigenetic events, characterized by consistent promoter hypermethylation of multiple tumor suppressor genes, points to the use of gene silencing mechanisms in the pathogenesis of recurrent respiratory papillomatosis.
Authors: Josena K Stephen; Kang Mei Chen; Misa Raitanen; Seija Grénman; Maria J Worsham Journal: Int J Gynecol Pathol Date: 2009-01 Impact factor: 2.762
Authors: Maria J Worsham; Kang Mei Chen; Josena K Stephen; Shaleta Havard; Michael S Benninger Journal: Otolaryngol Head Neck Surg Date: 2010-07 Impact factor: 3.497
Authors: Maria J Worsham; Josena K Stephen; Kang Mei Chen; Shaleta Havard; Veena Shah; Glendon Gardner; Vanessa G Schweitzer Journal: Cancer Lett Date: 2012-03-01 Impact factor: 8.679
Authors: Josena K Stephen; Kang Mei Chen; Veena Shah; Vanessa G Schweitzer; Glendon Gardner; Michael S Benninger; Maria J Worsham Journal: Int J Head Neck Surg Date: 2010-05
Authors: Josena K Stephen; Dhananjay Chitale; Vinod Narra; Kang Mei Chen; Raja Sawhney; Maria J Worsham Journal: Cancers (Basel) Date: 2011-06-01 Impact factor: 6.639
Authors: Maria J Worsham; Mei Lu; Kang Mei Chen; Josena K Stephen; Shaleta Havard; Vanessa P Schweitzer Journal: J Oncol Date: 2012-04-12 Impact factor: 4.375