Genetic and methylation status of CDKN2A (p14ARF/p16INK4A) and TP53 genes in recurrent respiratory papillomatosis.
Hum Pathol
; 119: 94-104, 2022 01.
Article
em En
| MEDLINE
| ID: mdl-34826422
ABSTRACT
Recurrent respiratory papillomatosis (RRP) is a rare and chronic disease affecting the upper airway with papillomatous lesions caused by the human papillomavirus (HPV) infection, especially HPV-6 and/or HPV-11 types. Little is known about the genetic and epigenetic drivers in RRP pathophysiology. For this purpose, we analyzed 27 papillomatous lesions from patients with RRP to evaluate somatic mutations and methylation status in CDKN2A (p14ARF/p16INK4A) and TP53, which are key tumor suppressor genes for the cell cycle control. Sanger sequencing analysis revealed one somatic mutation in TP53 (c.733_734insA) and four mutations in CDKN2A (c.-30G > T, c.29_30insA, c.69delT, and c.300C > A). These mutations were observed in 10 patients, 6 of which carried double mutation. Furthermore, 50% (5/10) of these patients carrying somatic mutations had RRP severity, representing 62.5% (5/8) of the severity cases in this study, albeit no significant association was found between somatic mutations and disease severity. Methylation-specific polymerase chain reaction assays revealed p14ARF promoter hypermethylation in 100% of cases, followed by TP53 (96.3%) and p16INK4A (55.6%), suggesting the influence of HPV in the DNA methylation machinery. In conclusion, somatic mutations were not common events identified in patients with RRP. However, epigenetic modulation by high methylation rates, particularly for the p14ARF/TP53 pathway, seems to be in the course of RRP development.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Contexto em Saúde:
2_ODS3
Problema de saúde:
2_enfermedades_transmissibles
Assunto principal:
Infecções Respiratórias
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Biomarcadores Tumorais
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Proteína Supressora de Tumor p53
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Metilação de DNA
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Inibidor p16 de Quinase Dependente de Ciclina
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Infecções por Papillomavirus
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Proteína Supressora de Tumor p14ARF
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Epigênese Genética
/
Mutação
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Adolescent
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Adult
/
Aged
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Child
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Child, preschool
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Hum Pathol
Assunto da revista:
PATOLOGIA
Ano de publicação:
2022
Tipo de documento:
Article