title: The epigenetic landscape of oral squamous cell carcinoma.
abstract: BACKGROUND
  There is relatively little methylation array data available specifically for oral squamous cell carcinoma (OSCC). This study aims to compare the DNA methylome across a large cohort of tumour/normal pairs.
  
  
  METHODS
  DNA was extracted from 44 OSCCs and paired normal mucosa. DNA methylation analysis employed the Illumina GoldenGate high-throughput array comprising 1505 CpG loci selected from 807 epigenetically regulated genes. This data was correlated with extracapsular spread (ECS), human papilloma virus (HPV) status, recurrence and 5-year survival.
  
  
  RESULTS
  Differential methylation levels of a number of genes distinguished the tumour tissue sample from the matched normal. Putative methylation signatures for ECS and recurrence were identified. The concept of concordant methylation or CpG island methylator phenotype (CIMP) in OSCC is supported by our data, with an association between 'CIMP-high' and worse prognosis. Epigenetic deregulation of NOTCH4 signalling in OSCC was also observed, as part of a possible methylation signature for recurrence, with parallels to recently discovered NOTCH mutations in HNSCC. Differences in methylation in HPV-driven cases were seen, but are less significant than that has been recently proposed in other series.
  
  
  CONCLUSIONS
  Although OSCC seems as much an 'epigenetic' as a genetic disease, the translational potential of cancer epigenetics has yet to be fully exploited. This data points to the application of epigenetic biomarkers and targets available to further the development of therapy in OSCC.
authors.affiliation: Liverpool Cancer Research UK Centre, Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, Block C, Waterhouse Buildings, Brownlow Street, University of Liverpool, Liverpool L69 3GL, UK. jithesh@liv.ac.uk
authors.forename: P V
authors.initials: PV
authors.lastname: Jithesh
authors.forename: J M
authors.initials: JM
authors.lastname: Risk
authors.forename: A G
authors.initials: AG
authors.lastname: Schache
authors.forename: J
authors.initials: J
authors.lastname: Dhanda
authors.forename: B
authors.initials: B
authors.lastname: Lane
authors.forename: T
authors.initials: T
authors.lastname: Liloglou
authors.forename: R J
authors.initials: RJ
authors.lastname: Shaw
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics*; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D030361:Papillomavirus Infections; D010641:Phenotype; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000074562:Receptor, Notch4; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C106075:NOTCH4 protein, human; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D000074562:Receptor, Notch4; D051880:Receptors, Notch