Common Docking Domain Mutation E322K of the ERK2 Gene is Infrequent in Oral Squamous Cell Carcinomas

Background: Mutations in the MAPK (Mitogen Activated Protein Kinase) signaling pathway - EGFR/Ras/RAF/MEK have been associated with the development of several carcinomas. ERK2, a downstream target of theMAPK pathway and a founding member of the MAPK family is activated by cellular signals emanating at the cellmembrane. Activated ERK2 translocates into the nucleus to transactivate genes that promote cell proliferation.MKP - a dual specific phosphatase - interacts with activated ERK2 via the common docking (CD) domain of thelater to inactivate (dephosphorylate) and effectively terminate further cell proliferation. A constitutively activeform of ERK2 carrying a single point mutation – E322K in its CD domain, was earlier reported by our laboratory.In the present study, we investigated the prevalence of this CD domain E322K mutation in 88 well differentiatedOSCC tissue samples. Materials and
Method: Genomic DNA specimens isolated from 88 oral squamous cellcarcinoma tissue samples were amplified with primers flanking the CD domain of the ERK2 gene. Subsequently,PCR amplicons were gel purified and subjected to direct sequencing to screen for mutations.
Results: Directsequencing of eighty eight OSCC samples identified an E322K CD domain mutation in only one (1.1%) OSCCsample.
Conclusions: Our result indicates that mutation in the CD domain of ERK2 is rare in OSCC patients,which suggests the role of genetic alterations in other mitogenic genes in the development of carcinoma in the restof the patients. Nevertheless, the finding is clinically significant, as the relatively rare prevalence of the E322Kmutation in OSCC suggests that ERK2, being a common end point signal in the multi-hierarchical mitogenactivated signaling pathway may be explored as a viable drug target in the treatment of OSCC.