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Genome Med. 2017 Apr 5;9(1):33. doi: 10.1186/s13073-017-0419-z.

Unique DNA methylation signature in HPV-positive head and neck squamous cell carcinomas.

Author information

1
Epigenetics Group, International Agency for Research on Cancer (IARC), 150 Cours Albert Thomas, 69008, Lyon, France. davide.degli-esposti@irstea.fr.
2
Epigenetics Group, International Agency for Research on Cancer (IARC), 150 Cours Albert Thomas, 69008, Lyon, France.
3
Instituto Nacional de Cancer, Rio de Janeiro, Brazil.
4
Université Côte d'Azur, CNRS, Inserm, Institut de Biologie Valrose (iBV), 06100, Nice, France.
5
Centre Antoine Lacassagne, Nice, 06189, France.
6
MTA-DE Public Health Research Group, University of Debrecen, Debrecen, Hungary.
7
Environment Section, International Agency for Research on Cancer (IARC), 150 Cours Albert Thomas, 69008, Lyon, France.
8
Infection Cancer Biology Group, International Agency for Research on Cancer (IARC), 150 Cours Albert Thomas, 69008, Lyon, France.
9
Université Côte d'Azur, Laboratoire de Virologie, CHU Nice-Archet, 06202, Nice, France.
10
Université Côte d'Azur, CNRS, Inserm, Institut de Biologie Valrose (iBV), 06100, Nice, France. Ellen.VAN-OBBERGHEN@unice.fr.
11
Centre Antoine Lacassagne, Nice, 06189, France. Ellen.VAN-OBBERGHEN@unice.fr.
12
Epigenetics Group, International Agency for Research on Cancer (IARC), 150 Cours Albert Thomas, 69008, Lyon, France. HercegZ@iarc.fr.

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.

KEYWORDS:

CpG shores; Differentially methylated regions; HPV; Head and neck squamous cell carcinomas; Predictive models

PMID:
28381277
PMCID:
PMC5382363
DOI:
10.1186/s13073-017-0419-z
[Indexed for MEDLINE]
Free PMC Article

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