title: A Novel Mutation in the DNA Binding Domain of NFKB is Associated with Speckled Leukoplakia.
abstract: BACKGROUND
  Activation and inactivation of nuclear factor of kappa light chain gene enhancer in B cells (NFKB) is tightly regulated to ensure effective onset and cessation of defensive inflammatory signaling. However, mutations within NFKB, or change in activation and inactivation molecules have been reported in a few cancers. Although oral squamous cell carcinoma is one of the most prevalent forms of cancer in India, with a development associated with malignant transformation of precancerous lesions, the genetic status of NFKB and relative rates of change in oral precancerous lesions remain unknown. Hence in the present study we investigated all twenty four exons of NFKB gene in two precancerous lesions, namely oral submucous fibrosis (OSMF) and oral leukoplakia (OL) to understand its occurrence, incidence and assess its possible contribution to malignant transformation.
  
  
  METHODS
  Chromosomal DNA isolated from twenty five each of OSMF and OL tissue biopsy samples were subjected to PCR amplification with intronic primers flanking twenty four exons of the NFKB gene. The PCR amplicons were subsequently subjected to direct sequencing to elucidate the mutation status.
  
  
  RESULTS
  Sequence analysis identified a novel heterozygous mutation, c.419T>A causing substitution of leucine with glutamine at codon 140 (L140Q) in an OL sample.
  
  
  CONCLUSIONS
  The identification of a substitution mutation L140Q within the DNA binding domain of NFKB in OL suggests that NFKB mutation may be relatively an early event during transformation. To the best of our knowledge, this study is the first to have identified a missense mutation in NFKB in OL.
authors: Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Sri Ramachandra University, Chennai, India Email : drarvindram@yahoo.co.in.
authors: Giri Valanthan Veda
authors: GV
authors: Govindarajan
authors: Lokesh
authors: L
authors: Bhanumurthy
authors: Anandh
authors: A
authors: Balasubramanian
authors: Arvind
authors: A
authors: Ramanathan
mesh_terms: D003430:Cross-Sectional Studies; D004247:DNA / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005091:Exons / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D007194:India; D007972:Leukoplakia, Oral / Q000235:genetics* / Q000473:pathology*; D009062:Mouth Neoplasms / Q000235:genetics / Q000473:pathology; D009154:Mutation / Q000235:genetics*; D016328:NF-kappa B / Q000235:genetics*; D009914:Oral Submucous Fibrosis / Q000235:genetics / Q000473:pathology; D016133:Polymerase Chain Reaction / Q000379:methods; D011230:Precancerous Conditions / Q000235:genetics / Q000473:pathology; D000072417:Protein Domains / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D016328:NF-kappa B; D004247:DNA