Unique DNA methylation signature in HPV-positive head and neck squamous cell carcinomas.
Genome Med
; 9(1): 33, 2017 04 05.
Article
em En
| MEDLINE
| ID: mdl-28381277
ABSTRACT
BACKGROUND:
Head and neck squamous cell carcinomas (HNSCCs) represent a heterogeneous group of cancers for which human papilloma virus (HPV) infection is an emerging risk factor. Previous studies showed promoter hypermethylation in HPV(+) oropharyngeal cancers, but only few consistent target genes have been so far described, and the evidence of a functional impact on gene expression is still limited.METHODS:
We performed global and stratified pooled analyses of epigenome-wide data in HNSCCs based on the Illumina HumanMethylation450 bead-array data in order to identify tissue-specific components and common viral epigenetic targets in HPV-associated tumours.RESULTS:
We identified novel differentially methylated CpGs and regions associated with viral infection that are independent of the anatomic site. In particular, most hypomethylated regions were characterized by a marked loss of CpG island boundaries, which showed significant correlations with expression of neighbouring genes. Moreover, a subset of only five CpGs in a few hypomethylated regions predicted HPV status with a high level of specificity in different cohorts. Finally, this signature was a better predictor of survival compared with HPV status determined by viral gene expression by RNA sequencing in The Cancer Genome Atlas cohort.CONCLUSIONS:
We identified a novel epigenetic signature of HPV infection in HNSCCs which is independent of the anatomic site, is functionally correlated with gene expression and may be leveraged for improved stratification of prognosis in HNSCCs.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Carcinoma de Células Escamosas
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Regiões Promotoras Genéticas
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Metilação de DNA
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Infecções por Papillomavirus
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Neoplasias de Cabeça e Pescoço
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article