Molecular profile of nasopharyngeal carcinoma: analysing tumour suppressor gene promoter hypermethylation by multiplex ligation-dependent probe amplification

Ooft, M. L., van Ipenburg, J., van Loo, R., de Jong, R., Moelans, C., Braunius, W., de Bree, R., van Diest, P., Koljenović, S., Baatenburg de Jong, R., Hardillo, J. & Willems, S. M., Apr-2018, In : Journal of Clinical Pathology. 71, 4, p. 351-359 9 p.

Research output: Contribution to journalArticleAcademicpeer-review

Copy link to clipboard


  • Molecular profile of nasopharyngeal carcinoma

    Final publisher's version, 1.49 MB, PDF document

    Request copy


  • Marc L Ooft
  • Jolique van Ipenburg
  • Rob van Loo
  • Rick de Jong
  • Cathy Moelans
  • Weibel Braunius
  • Remco de Bree
  • Paul van Diest
  • Senada Koljenović
  • Rob Baatenburg de Jong
  • Jose Hardillo
  • Stefan M Willems

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.

Original languageEnglish
Pages (from-to)351-359
Number of pages9
JournalJournal of Clinical Pathology
Issue number4
Publication statusPublished - Apr-2018
Externally publishedYes


  • Adult, Aged, Carcinoma/genetics, Carcinoma, Squamous Cell/genetics, DNA Methylation/genetics, Epstein-Barr Virus Infections/complications, Female, Gene Expression Profiling, Genes, Tumor Suppressor, Head and Neck Neoplasms/genetics, Humans, Male, Middle Aged, Multiplex Polymerase Chain Reaction, Nasopharyngeal Carcinoma, Nasopharyngeal Neoplasms/genetics, Promoter Regions, Genetic/genetics, Squamous Cell Carcinoma of Head and Neck, Transcriptome

ID: 124013001