A Novel Heterozygous Mutation (F252Y) in Exon 7 of the IRF6 Gene is Associated with Oral Squamous Cell Carcinomas

Background: Interferon regulatory factor 6 (IRF6) is a transcription factor with distinct and conserved DNAand protein binding domains. Mutations within the protein binding domain have been significantly observedin subjects with orofacial cleft relative to healthy controls. In addition, recent studies have identified loss ofexpression of IRF6 due to promoter hypermethylation in cutaneous squamous cell carcinomas. Since mutationalevents occurring within the conserved domains are likely to affect the function of a protein, we investigatedwhether regions within the IRF6 gene that encodes for the conserved protein binding domain carried mutationsin oral squamous cell carcinoma (OSCC). Materials and
Methods: Total chromosomal DNA extracted from32 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 weresubsequently 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 occurredin heterozygous condition in 9% (3/32) of OSCC samples. The wild type codon TTC at position 252 coding forphenylalanine was found to be mutated to TAC that coded for tyrosine (F252Y).
Conclusions: The present studyidentified for the first time a novel mutation within the conserved protein binding domain of IRF6 gene in tissuesamples of subjects with OSCC.