title: Tyrosine 1045 codon mutations in exon 27 of EGFR are infrequent in oral squamous cell carcinomas.
abstract: BACKGROUND
  The activation and inactivation of receptor tyrosine kinases are tightly regulated to ensure faithful replication of cells. After having transduced extracellular growth activating signals, activated EGFR is subjected to downregulation either by clathrin mediated endocytosis or c-Cbl mediated proteasome degradation depending on the ligand concentration. c-Cbl is an ubiquitin ligase which requires a phosphorylated tyrosine residue at position 1045 in the cytoplasmic domain of EGFR to interact and add ubiquitin molecules. While activating mutations in exons 19 and 21 have been associated with the development of several cancers, the status of mutations at tyrosine 1045 coding exon 27 of EGFR remain to be investigated. Consistently, defective phosphorylation at 1045 has been associated with sustained phosphorylation of EGFR in non-small lung carcinomas. Hence in the present study we investigated the genetic status of the tyrosine 1045 coding site within exon 27 of EGFR gene to explore for possible occurrence of mutations in this region, especially since no studies have addressed this issue so far.
  
  
  METHODS
  Tumor chromosomal DNA isolated from thirty five surgically excised oral squamous cell carcinoma tissues was subjected to PCR amplification with intronic primers flanking the tyrosine 1045 coding exon 27 of EGFR gene. The PCR amplicons were subsequently subjected to direct sequencing to elucidate the mutation status.
  
  
  RESULTS
  Sequence analysis identified no mutations in the tyrosine 1045 codon of EGFR in any of the thirty five samples that were analyzed.
  
  
  CONCLUSIONS
  The lack of identification of mutation in the tyrosine 1045 codon of EGFR suggests that mutations in this region may be relatively rare in oral squamous cell carcinomas. To the best of our knowledge, this study is the first to have explored the genetic status of exon 27 of EGFR in oral squamous cell carcinoma tissue samples.
authors.affiliation: Human Genetics Laboratory, Sree Balaji Medical and Dental College and Hospital, Bharath University, Chennai, India. drarvindram@yahoo.co.in
authors.forename: Mehta Dhaval
authors.initials: MD
authors.lastname: Tushar
authors.forename: Arvind
authors.initials: A
authors.lastname: Ramanathan
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D003062:Codon / Q000235:genetics*; D003430:Cross-Sectional Studies; D004273:DNA, Neoplasm / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics*; D005091:Exons / Q000235:genetics*; D006801:Humans; D009062:Mouth Neoplasms / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D014443:Tyrosine / Q000235:genetics*
chemical_list: D003062:Codon; D004273:DNA, Neoplasm; D014443:Tyrosine; C512478:EGFR protein, human; D066246:ErbB Receptors