CORRELATION BETWEEN K-RAS GENE MUTATION AND PROGNOSIS OF PATIENTS WITH NONSMALL CELL LUNG-CARCINOMA

BACKGROUND. Mutations at codons 12, 13, and 61 of the three ms genes, H-ras, K-rns, and N-ras, convert these genes into active oncogenes. It appears that ras gene mutations can be found in a variety of tumor ty pes. The purpose of this study was to evaluate the clinical significan ce of K-ras gene mutation in nonsmall cell lung carcinoma (NSCLC). MET HODS, The authors analyzed 58 NSCLC patients for mutations at codons 1 2, 13, and 61 of tile K-ras gene and correlated the findings with the tumor stage and patient survival. Polymerase chain reaction-single str and conformation poll morphism (PCR-SSCP) and the direct nucleotide se quencing method were used to detect mutations after amplification of m s specific sequences bg PCR. RESULTS, Fourteen mutations (24%) of ras genes were found, all at codon 12 of che R-ms gene. GGT to GAT transit ion was the predominant mutational pattern. There was a significant as sociation between K-rus mutation and the tumor stage (i.e., the higher the stage, the higher the mutation rate) (P = 0.014). Using univariat e analysis, the presence of K-ras mutation in paraffin embedded tissue from patients who received treatment with curative intent was associa ted with a shorter survival (P = 0.039). Tile median survival duration for patients with or without K-ras mutation was 9 and 30 months, resp ectively The Cos proportional hazards model also predicted a higher ri sk for patients with K-ras mutations (P = 0.047), CONCLUSIONS. K-rns m utations, present in a subset of NSCLC, are associated with tumor prog ression and shortened patient survival. (C) 1997 American Cancer Socie ty.