title: A novel heterozygous mutation (F252Y) in exon 7 of the IRF6 gene is associated with oral squamous cell carcinomas.
abstract: BACKGROUND
  Interferon regulatory factor 6 (IRF6) is a transcription factor with distinct and conserved DNA and protein binding domains. Mutations within the protein binding domain have been significantly observed in subjects with orofacial cleft relative to healthy controls. In addition, recent studies have identified loss of expression of IRF6 due to promoter hypermethylation in cutaneous squamous cell carcinomas. Since mutational events occurring within the conserved domains are likely to affect the function of a protein, we investigated whether regions within the IRF6 gene that encodes for the conserved protein binding domain carried mutations in oral squamous cell carcinoma (OSCC).
  
  
  METHODS
  Total chromosomal DNA extracted from 32 post surgical OSCC tissue samples were amplified using intronic primers flanking the exon 7 of IRF6 gene, which encodes for the major region of protein binding domain. The PCR amplicons from all the samples were subsequently resolved in a 1.2% agarose gel, purified and subjected to direct sequencing to screen for mutations.
  
  
  RESULTS
  Sequencing analysis resulted in the identification of a mutation within exon 7 of IRF6 that occurred in heterozygous condition in 9% (3/32) of OSCC samples. The wild type codon TTC at position 252 coding for phenylalanine was found to be mutated to TAC that coded for tyrosine (F252Y).
  
  
  CONCLUSIONS
  The present study identified for the first time a novel mutation within the conserved protein binding domain of IRF6 gene in tissue samples of subjects with OSCC.
authors.affiliation: Department of Periodontology, Mahe Institute of Dental Sciences, Union Territory of Pondichery, India E-mail : drarvindram@yahoo.co.in.
authors.forename: Anil
authors.initials: A
authors.lastname: Melath
authors.forename: Gopi Krishnan
authors.initials: GK
authors.lastname: Santhakumar
authors.forename: Shyam Sunder
authors.initials: SS
authors.lastname: Madhavannair
authors.forename: Binoy Mathews
authors.initials: BM
authors.lastname: Nedumgottil
authors.forename: Arvind
authors.initials: A
authors.lastname: Ramanathan
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D003430:Cross-Sectional Studies; D004247:DNA / Q000235:genetics; D005091:Exons / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics*; D009062:Mouth Neoplasms / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011379:Prognosis
chemical_list: C109803:IRF6 protein, human; D050835:Interferon Regulatory Factors; D004247:DNA