Tyrosine 1045 Codon Mutations in Exon 27 of EGFR are Infrequent in Oral Squamous Cell Carcinomas

Abstract

<b>Background:</b> The activation and inactivation of receptor tyrosine kinases are tightly regulated to ensure faithfulreplication of cells. After having transduced extracellular growth activating signals, activated EGFR is subjectedto downregulation either by clathrin mediated endocytosis or c-Cbl mediated proteasome degradation dependingon the ligand concentration. c-Cbl is an ubiquitin ligase which requires a phosphorylated tyrosine residue atposition 1045 in the cytoplasmic domain of EGFR to interact and add ubiquitin molecules. While activatingmutations in exons 19 and 21 have been associated with the development of several cancers, the status of mutationsat tyrosine 1045 coding exon 27 of EGFR remain to be investigated. Consistently, defective phosphorylation at1045 has been associated with sustained phosphorylation of EGFR in non-small lung carcinomas. Hence in thepresent study we investigated the genetic status of the tyrosine 1045 coding site within exon 27 of EGFR geneto explore for possible occurrence of mutations in this region, especially since no studies have addressed thisissue so far. Materials and <br/><b>Methods</b>: Tumor chromosomal DNA isolated from thirty five surgically excised oralsquamous cell carcinoma tissues was subjected to PCR amplification with intronic primers flanking the tyrosine1045 coding exon 27 of EGFR gene. The PCR amplicons were subsequently subjected to direct sequencing toelucidate the mutation status. <br/><b>Results</b>: Sequence analysis identified no mutations in the tyrosine 1045 codon ofEGFR in any of the thirty five samples that were analyzed. <br/><b>Conclusions</b>: The lack of identification of mutation inthe tyrosine 1045 codon of EGFR suggests that mutations in this region may be relatively rare in oral squamouscell carcinomas. To the best of our knowledge, this study is the first to have explored the genetic status of exon27 of EGFR in oral squamous cell carcinoma tissue samples.