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 ras genes, H-ras, K-ras, and N-ras, convert these genes into active oncogenes. It appears that ras gene mutations can be found in a variety of tumor types. The purpose of this study was to evaluate the clinical significance of K-ras gene mutation in nonsmall cell lung carcinoma (NSCLC).


METHODS
The authors analyzed 58 NSCLC patients for mutations at codons 12, 13, and 61 of the K-ras gene and correlated the findings with the tumor stage and patient survival. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and the direct nucleotide sequencing method were used to detect mutations after amplification of ras specific sequences by PCR.


RESULTS
Fourteen mutations (24%) of ras genes were found, all at codon 12 of the K-ras gene. GGT to GAT transition was the predominant mutational pattern. There was a significant association between K-ras mutation and the tumor stage (i.e., the higher the stage, the higher the mutation rate) (P = 0.014). Using univariate analysis, the presence of K-ras mutation in paraffin embedded tissue from patients who received treatment with curative intent was associated with a shorter survival (P = 0.039). The median survival duration for patients with or without K-ras mutation was 9 and 30 months, respectively. The Cox proportional hazards model also predicted a higher risk for patients with K-ras mutations (P = 0.047).


CONCLUSIONS
K-ras mutations, present in a subset of NSCLC, are associated with tumor progression and shortened patient survival.
Cho
J Y
JY
Yonsei Cancer Center, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.
Kim
J H
JH
Lee
Y H
YH
Chung
K Y
KY
Kim
S K
SK
Gong
S J
SJ
You
N C
NC
Chung
H C
HC
Roh
J K
JK
Kim
B S
BS
D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D015342:DNA Probes; D018450:Disease Progression; D005260:Female; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011379:Prognosis; D016019:Survival Analysis
D015342:DNA Probes