title: Mutation Analysis of the Dimer Forming Domain of the Caspase 8 Gene in Oral Submucous Fibrosis and Squamous Cell Carcinomas.
abstract: BACKGROUND
  Missense and frame-shift mutations within the dimer forming domain of the caspase 8 gene have been identified in several cancers. However, the genetic status of this region in precancerous lesions, like oral submucous fibrosis (OSMF), and well differentiated oral squamous cell carcinomas (OSCCs) in patients from southern region of India is not known, and hence the present study was designed to address this issue.
  
  
  METHODS
  Genomic DNA isolated from biopsy tissues of thirty one oral submucous fibrosis and twenty five OSCC samples were subjected to PCR amplification with intronic primers flanking exon 7 of the caspase 8 gene. The PCR amplicons were subsequently subjected to direct sequencing to elucidate the status of mutation.
  
  
  RESULTS
  Sequence analysis identified a frame-shift and a novel missense mutation in two out of twenty five OSCC samples. The frame-shift mutation was due to a two base pair deletion (c.1225_1226delTG), while the missense mutation was due to substitution of wild type cysteine residue with phenylalanine at codon 426 (C426F). The missense mutation, however, was found to be heterozygous as the wild type C426C codon was also present. None of the OSMF samples carried mutations.
  
  
  CONCLUSIONS
  The identification of mutations in OSCC lesions but not OSMF suggests that dimer forming domain mutations in caspase 8 may be limited to malignant lesions. The absence of mutations in OSMF also suggests that the samples analyzed in the present study may not have acquired transforming potential. To the best of our knowledge this is the first study to have explored and identified frame-shift and novel missense mutations in OSCC tissue samples.
authors.affiliation: Department of Oral Medicine and Radiology, Faculty of Dentistry, SRM University, Ramapuram, India E-mail : arvind@ebl.org.in.
authors.forename: Uthara
authors.initials: U
authors.lastname: Menon
authors.forename: Poongodi
authors.initials: P
authors.lastname: V
authors.forename: Pitty Hari
authors.initials: PH
authors.lastname: Raghuram
authors.forename: Kannan
authors.initials: K
authors.lastname: Kannan
authors.forename: Giri Valanthan Veda
authors.initials: GV
authors.lastname: Govindarajan
authors.forename: Arvind
authors.initials: A
authors.lastname: Ramanathan
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D053181:Caspase 8 / Q000235:genetics*; D004252:DNA Mutational Analysis; D017931:DNA Primers; D005091:Exons / Q000235:genetics*; D016368:Frameshift Mutation / Q000235:genetics*; D006801:Humans; D007194:India; D009062:Mouth Neoplasms / Q000235:genetics* / Q000473:pathology; D020125:Mutation, Missense / Q000235:genetics*; D009367:Neoplasm Staging; D009914:Oral Submucous Fibrosis / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D011379:Prognosis; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary
chemical_list: D017931:DNA Primers; C505530:CASP8 protein, human; D053181:Caspase 8