RT Journal Article
SR Electronic
T1 Molecular profile of nasopharyngeal carcinoma: analysing tumour suppressor gene promoter hypermethylation by multiplex ligation-dependent probe amplification
JF Journal of Clinical Pathology
JO J Clin Pathol
FD BMJ Publishing Group Ltd and Association of Clinical Pathologists
SP 351
OP 359
DO 10.1136/jclinpath-2017-204661
VO 71
IS 4
A1 Marc L Ooft
A1 Jolique van Ipenburg
A1 Rob van Loo
A1 Rick de Jong
A1 Cathy Moelans
A1 Weibel Braunius
A1 Remco de Bree
A1 Paul van Diest
A1 Senada Koljenović
A1 Rob Baatenburg de Jong
A1 Jose Hardillo
A1 Stefan M Willems
YR 2018
UL http://jcp.bmj.com/content/71/4/351.abstract
AB 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.