title: Identification of FOXM1-induced epigenetic markers for head and neck squamous cell carcinomas.
abstract: BACKGROUND
  Epigenetic reprogramming of the methylome has been implicated in all stages of cancer evolution. It is now well accepted that cancer cells exploit epigenetic reprogramming, a mechanism that regulates stem/progenitor cell renewal and differentiation, to promote cancer initiation and progression. The oncogene FOXM1 has been implicated in all major forms of human cancer.
  
  
  METHODS
  We have recently shown that aberrant upregulation of FOXM1 orchestrated a DNA methylation signature that mimics the cancer methylome landscape, from which we have identified a number of FOXM1-induced epigenetic markers. Differential promoter methylation and gene expression in clinical specimens were measured using commercially available bisulfite conversion kits and absolute quantitative PCR, respectively.
  
  
  RESULTS
  Here, we investigated 8 FOXM1-induced differentially methylated genes, SPCS1, FLNA, CHPF, GLT8D1, C6orf136, MGAT1, NDUFA10, and PAFAH1B3, using human head and neck tissue specimens donated by 2 geographically independent patient cohorts from Norway and the United Kingdom. Two genes (GLT8D1 and C6orf136) were found to be differentially expressed in head and neck squamous cell carcinomas (HNSCCs). Using methylation-specific quantitative PCR, we confirmed that the promoters of GLT8D1 and C6orf136 were hypo- and hypermethylated, respectively, in HNSCC tissues.
  
  
  CONCLUSIONS
  Given that epigenetic change precedes gene expression, methylation status of candidate genes identified from this study may represent a signature of premalignancy, rendering them potentially useful predictive biomarkers for precancer screening and/or therapeutic targets for cancer prevention.
authors.affiliation: Centre for Clinical and Diagnostic Oral Sciences, Institute of Dentistry, Barts & The London School of Medicine and Dentistry, Queen Mary University of London, England, United Kingdom.
authors.forename: Sungjae
authors.initials: S
authors.lastname: Hwang
authors.forename: Swarna
authors.initials: S
authors.lastname: Mahadevan
authors.forename: Fatima
authors.initials: F
authors.lastname: Qadir
authors.forename: Iain L
authors.initials: IL
authors.lastname: Hutchison
authors.forename: Daniela Elena
authors.initials: DE
authors.lastname: Costea
authors.forename: Evelyn
authors.initials: E
authors.lastname: Neppelberg
authors.forename: Per Gunnar
authors.initials: PG
authors.lastname: Liavaag
authors.forename: Ahmad
authors.initials: A
authors.lastname: Waseem
authors.forename: Muy-Teck
authors.initials: MT
authors.lastname: Teh
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D016695:Glycosyltransferases / Q000235:genetics; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009664:Norway; D011401:Promoter Regions, Genetic; D012189:Retrospective Studies; D000077195:Squamous Cell Carcinoma of Head and Neck; D006113:United Kingdom; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; C000592012:GLT8D1 protein, human; D016695:Glycosyltransferases
keywords: FOXM1; biomarkers; biopsy; cancer epigenetics; diagnostic; epigenome; methylome; promoter methylation; reprogramming; squamous cell carcinoma; tissue