Lack of RING Finger Domain (RFD) Mutations of the c-CblGene in Oral Squamous Cell Carcinomas in Chennai, India

Abstract

<b>Background:</b> In normal cells, activated epidermal growth factor receptor (EGFR) molecules are subjected toubiquitination-mediated proteasome degradation pathway by c-Cbl, an ubiquitin ligase that checks uncontrolledproliferation. Hence expression of wild type c-Cbl molecule is essential to keep this degradation machinery in afunctional state. Loss of expression or function of c-Cbl may consequently lead to sustained activation of EGFRand promote carcinogenesis, loss of function mutations in the c-Cbl gene already being reported in lung andhematopoietic cancers. However, the genetic status of c-Cbl in oral squamous cell carcinoma (OSCC) is notknown. Hence in the present study we investigated the genomic DNA isolated from OSCC tissue biopsy samplesfor mutations in the RING finger domain coding region of c-Cbl gene, which has also been reported to be mostfrequently mutated in other cancers. Materials and <br/><b>Methods</b>: Total genomic DNA isolated from thirty two postsurgical OSCC tissue samples were amplified using primers flanking the exon 8 of c-Cbl gene that codes for theRING finger domain. The PCR amplicons were then resolved in a 1.2% agarose gel, purified and subjected todirect sequencing to screen for mutations. <br/><b>Results</b>: The sequencing data of the thirty two OSCC samples didnot identify mutations in the RING finger domain coding region of c-Cbl gene. <br/><b>Conclusions</b>: To the best of ourknowledge, this is the first time that the genetic status of c-Cbl gene in OSCC samples has been investigated. Thepresent data indicates that genetic alteration of RING finger domain coding region of c-Cbl gene is relativelyinfrequent in OSCC samples.