title: Promoter hypermethylation using 24-gene array in early head and neck cancer: better outcome in oral than in oropharyngeal cancer.
abstract: 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.
authors.affiliation: Department of Oral and Maxillofacial Surgery; University Medical Center Utrecht; Utrecht, the Netherlands.
authors.forename: Rob
authors.initials: R
authors.lastname: Noorlag
authors.affiliation: Department of Otorhinolaryngology; University Medical Center Utrecht; Utrecht, the Netherlands.
authors.forename: Pauline M W
authors.initials: PM
authors.lastname: van Kempen
authors.affiliation: Department of Pathology; University Medical Center Utrecht; Utrecht, the Netherlands.
authors.forename: Cathy B
authors.initials: CB
authors.lastname: Moelans
authors.affiliation: Department of Pathology; University Medical Center Utrecht; Utrecht, the Netherlands.
authors.forename: Rick
authors.initials: R
authors.lastname: de Jong
authors.affiliation: Department of Pathology; University Medical Center Utrecht; Utrecht, the Netherlands.
authors.forename: Laura E R
authors.initials: LE
authors.lastname: Blok
authors.affiliation: Department of Oral and Maxillofacial Surgery; University Medical Center Utrecht; Utrecht, the Netherlands.
authors.forename: Ronald
authors.initials: R
authors.lastname: Koole
authors.affiliation: Department of Otorhinolaryngology; University Medical Center Utrecht; Utrecht, the Netherlands.
authors.forename: Wilko
authors.initials: W
authors.lastname: Grolman
authors.affiliation: Department of Pathology; University Medical Center Utrecht; Utrecht, the Netherlands.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: van Diest
authors.affiliation: Department of Oral and Maxillofacial Surgery; University Medical Center Utrecht; Utrecht, the Netherlands.
authors.forename: Robert J J
authors.initials: RJ
authors.lastname: van Es
authors.affiliation: Department of Pathology; University Medical Center Utrecht; Utrecht, the Netherlands.
authors.forename: Stefan M
authors.initials: SM
authors.lastname: Willems
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019175:DNA Methylation; D018572:Disease-Free Survival; D005260:Female; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D009959:Oropharyngeal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011401:Promoter Regions, Genetic; D000077195:Squamous Cell Carcinoma of Head and Neck; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor
keywords: DNA Methylation; Head Neck Cancer; Oral Cancer; Oropharyngeal Cancer; Prognosis; Squamous Cell Carcinoma; Tumor Suppressor Gene; hypermethylation