Marc L Ooft 1 , Jolique van Ipenburg 2 , Rob van Loo 1 , Rick de Jong 1 , Cathy Moelans 1 , Weibel Braunius 3,4 , Remco de Bree 4 , Paul van Diest 1 , Senada Koljenović 2 , Rob Baatenburg de Jong 5 , Jose Hardillo 5 , Stefan M Willems 1 Show Affiliations »
Abstract
AIMS: To assess differences in methylation profiles, and thus pathogenesis, between Epstein-Barr virus (EBV)-positive and negative nasopharyngeal carcinomas (NPCs). Also, promoter hypermethylation is a common phenomenon in early carcinogenesis to inactivate tumour suppressor genes. Since epigenetic changes are reversible, the therapeutic application of methylation inhibitors could provide treatment options. METHODS: We evaluated promoter hypermethylation profiles of 22 common tumour suppressor genes in 108 NPCs using methylation-specific multiplex ligation-dependent probe amplification. Correlation between methylation, clinicopathological features (including EBV) and survival was examined. Cluster analysis was also performed. RESULTS: Hypermethylation of RASSF1A and ESR1 was significantly more frequent in EBV-positive NPC, while hypermethylation of DAPK1 was more frequent in EBV-negative NPC. In logistic regression, age, with EBV-positive NPC occurring at earlier age, and RASSF1, with RASSF1 hypermethylation being more frequent in EBV-positive NPC, remained significant. In EBV-positive NPC, hypermethylation of RASSF1A predicted worse overall survival (OS) (HR 3.058,95% CI 1.027 to 9.107). In EBV-negative NPC, hypermethylated adenomatous polyposis coli (APC) was a predictor of poor disease-free survival (DFS) (HR 6.868, 95% CI 2.142 to 22.022). CONCLUSION: There are important epigenetic differences between EBV-negative and EBV-positive NPCs, with EBV-negative NPC having a more similar hypermethylation profile to other head and neck squamous cell carcinomas than EBV-positive NPC. Hypermethylation of RASSF1A might contribute to worse OS in EBV-positive NPC, and may be an important event in the pathogenesis of EBV-infected NPC. Hypermethylation of APC might contribute to worse DFS in EBV-negative NPC. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
AIMS: To assess differences in methylation profiles, and thus pathogenesis, between Epstein-Barr virus (EBV )-positive and negative nasopharyngeal carcinomas (NPCs). Also, promoter hypermethylation is a common phenomenon in early carcinogenesis to inactivate tumour suppressor genes. Since epigenetic changes are reversible, the therapeutic application of methylation inhibitors could provide treatment options. METHODS: We evaluated promoter hypermethylation profiles of 22 common tumour suppressor genes in 108 NPCs using methylation-specific multiplex ligation-dependent probe amplification. Correlation between methylation, clinicopathological features (including EBV ) and survival was examined. Cluster analysis was also performed. RESULTS: Hypermethylation of RASSF1A and ESR1 was significantly more frequent in EBV -positive NPC, while hypermethylation of DAPK1 was more frequent in EBV -negative NPC. In logistic regression, age, with EBV -positive NPC occurring at earlier age, and RASSF1, with RASSF1 hypermethylation being more frequent in EBV -positive NPC, remained significant. In EBV -positive NPC, hypermethylation of RASSF1A predicted worse overall survival (OS) (HR 3.058,95% CI 1.027 to 9 .107). In EBV -negative NPC, hypermethylated adenomatous polyposis coli (APC ) was a predictor of poor disease-free survival (DFS) (HR 6.868, 95% CI 2.142 to 22.022). CONCLUSION: There are important epigenetic differences between EBV -negative and EBV -positive NPCs, with EBV -negative NPC having a more similar hypermethylation profile to other head and neck squamous cell carcinomas than EBV -positive NPC. Hypermethylation of RASSF1A might contribute to worse OS in EBV -positive NPC, and may be an important event in the pathogenesis of EBV-infected NPC . Hypermethylation of APC might contribute to worse DFS in EBV -negative NPC. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Entities: Disease
Species
Keywords:
molecular oncology; molecular pathology; oncology; tumour Virology; tumour biology
Mesh： See more »
Year: 2017
PMID： 28893862 DOI： 10.1136/jclinpath-2017-204661
Source DB: PubMed Journal: J Clin Pathol ISSN： 0021-9746 Impact factor: 3.411