Promoter hypermethylation using 24-gene array in early head and neck cancer Better outcome in oral than in oropharyngeal cancer

作者：Noorlag Rob; van Kempen Pauline M W; Moelans Cathy B; de Jong Rick; Blok Laura E R; Koole Ronald; Grolman Wilko; van Diest Paul J; van Es Robert J J; Willems Stefan M^*

来源：Epigenetics, 2014, 9(9): 1220-1227.

DOI：10.4161/epi.29785

• hypermethylation
• Squamous Cell Carcinoma
• Tumor Suppressor Gene
• Head Neck Cancer
• Oral Cancer
• Oropharyngeal Cancer
• DNA Methylation
• Prognosis

Silencing of tumor suppressor genes (TSGs) by DNA promoter hypermethylation is an early event in carcinogenesis and a potential target for personalized cancer treatment. In head and neck cancer, little is known about the role of promoter hypermethylation in survival. Using methylation specific multiplex ligation-dependent probe amplification (MS-MLPA) we investigated the role of promoter hypermethylation of 24 well-described genes (some of which are classic TSGs), which are frequently methylated in different cancer types, in 166 HPV-negative early oral squamous cell carcinomas (OSCC), and 51 HPV-negative early oropharyngeal squamous cell carcinomas (OPSCC) in relation to clinicopathological features and survival. Early OSCC showed frequent promoter hypermethylation in RARB (31% of cases), CHFR (20%), CDH13 (13%), DAPK1 (12%), and APC (10%). More hypermethylation (>= 2 genes) independently correlated with improved disease specific survival (hazard ratio 0.17, P = 0.014) in early OSCC and could therefore be used as prognostic biomarker. Early OPSCCs showed more hypermethylation of CDH13 (58%), TP73 (14%), and total hypermethylated genes. Hypermethylation of two or more genes has a significantly different effect on survival in OPSCC compared with OSCC, with a trend toward worse instead of better survival. This could have a biological explanation, which deserves further investigation and could possibly lead to more stratified treatment in the future.

• 出版日期2014-9