title: Quantitative study of epigenetic signature in head and neck squamous cell carcinoma.
abstract: OBJECTIVE
  The aberrant upregulation of Forkhead box protein M1 (FOXM1) plays a fundamental role in cancer initiation by perturbing stem cell differentiation. This study aims to investigate the role of FOXMI in epigenetic modification and gene expression of target genes in primary human oral keratinocytes, squamous cell carcinoma cell lines, and head and neck squamous cell carcinoma (HNSCC) tissue biopsies.
  
  
  METHODS
  A genome-wide promoter methylation microarray was used to compare HNSCC cell line (n = 8), primary human oral keratinocytes (NOK; n = 8) transduced with FOXM1 and EGFP, and HNSCC tissue biopsies (n = 3). Seventeen Foxm1B- induced differentially methylated genes were shortlisted. An absolute quantitative polymerase chain reaction was used to validate the differential promoter DNA methylation of each candidate gene induced by FOXML. These results were compared with the methylation status and altered gene expressions of candidate genes in a panel of genomic DNA and messenger RNA (mRNA) samples previously extracted from HNSCC tissue biopsies.
  
  
  RESULTS
  The results were consistent with our hypothesis, showing that aberrant. upregulation of FOXM1 expression in in vitro primary NOK induces a global hypomethylation pattern similar to the HNSCC cell line and has an inverse correlation with in vivo mRNA expression levels of HNSCC tissue biopsy.
  
  
  CONCLUSIONS
  Such epigenetic changes have tremendous clinical potential as biomarkers for early cancer detection and therapeutic interventions.
authors.forename: Ayesha
authors.initials: A
authors.lastname: Umair
authors.forename: Bassel
authors.initials: B
authors.lastname: Tarakji
authors.forename: Alzoghaibi
authors.initials: A
authors.lastname: Ibrahim
authors.forename: Azzeghaibi
authors.initials: A
authors.lastname: Nasser
authors.forename: Alenzi
authors.initials: A
authors.lastname: Fq
authors.forename: Ayesha
authors.initials: A
authors.lastname: Shreen
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000235:genetics*; D055106:Genome-Wide Association Study; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000473:pathology; D006801:Humans; D015603:Keratinocytes / Q000473:pathology*; D009061:Mouth Mucosa / Q000473:pathology*; D000077195:Squamous Cell Carcinoma of Head and Neck; D014157:Transcription Factors / Q000235:genetics
chemical_list: C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; D014157:Transcription Factors