期刊
GENOME MEDICINE
卷 9, 期 -, 页码 -出版社
BIOMED CENTRAL LTD
DOI: 10.1186/s13073-017-0419-z
关键词
Head and neck squamous cell carcinomas; HPV; Differentially methylated regions; CpG shores; Predictive models
资金
- French National Institute of Cancer (INCA France)
- Fondation ARC
- Ligue Nationale Contre le Cancer [PAIR-VADS11-023]
- Epigenetic Group at International Agency for Cancer Research
- Fonds National de la Recherche, Luxembourg [10100060]
- IARC postdoctoral fellowship
- Marie Curie Actions People-COFUND
- Education Department of the Basque Government [POS_2014_1_102]
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 Human Methylation450 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.
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