RAS gene mutations and histomorphometric measurements in oral squamous cell carcinoma

Members of the RAS gene family frequently are mutated in cancers including oral squamous cell carcinoma (OSCC). We investigated the correlation of histological characteristics of OSCC with RAS gene mutations. We graded tumors and extracted genomic DNA from OSCC. The first two exons of KRAS, HRAS and NRAS genes were subjected to PCR amplification and DNA sequencing followed by bioinformatic analysis to explore the structural and functional impact of the mutations on encoding of proteins. Cellular and nuclear diameters in histological sections were varied in all grades of cancer. Using sequence analysis, we identified nonsynonymous mutations in both HRAS (G12S, G15C, D54H, Q61H, Q61L, E62D, E63D, Q70E, Q70V) and NRAS (Q22P, K88R). Stop codon mutations, however, were observed in KRAS. Spatial orientation of substituted amino acids was observed despite conservation of overall structure of variant proteins. Our findings suggest that KRAS may be mutated more frequently in OSCC compared to HRAS and NRAS. Also, the histological features of nuclear and cellular diameter differed significantly between the KRAS mutated and unmutated cases.