Prognostic impact of mutated K-ras gene in surgically resected non-small cell lung cancer patients.
Mutated K-ras oncogenes have been detected in a third of lung adenocarcinomas, located usually in codon 12, its presence correlating negatively with survival. To further define the role of K-ras point mutations in non-small cell lung cancer, we studied the presence of mutated K-ras genes in surgical specimens from 66 patients. Polymerase chain reaction was performed from sections of formalin-fixed paraffin-embedded tissue. We screened for point mutations in codons 12, 13 and 61 of the K-ras gene by dot blot hybridization analysis with mutation-specific oligonucleotide probes. Ras gene mutations were present in 13 of 66 carcinomas (20%), nine in codon 12 and four in codon 61. Three squamous cell carcinomas harbored two different point mutations in K-ras codon 12. Mutated K-ras genes were found more frequently in squamous cell carcinomas (eight of 38) than in adenocarcinoma (three of 22). Analysis of nucleotide sequence disclosed a multifarious mutation pattern of K-ras codon 12, where the most common conversion was from glycine (GGT) to valine (GTT). K-ras point mutation positive subset had poorer survival, nine of the 13 patients died during the follow-up period as compared with 22 of 53 patients with no mutation in the K-ras gene (P = 0.01). The difference was also strikingly significant when stratified according to node status.
Department of Medical Oncology, University Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain.
R
R
Rosell
S
S
Li
Z
Z
Skacel
J L
JL
Mate
J
J
Maestre
M
M
Canela
E
E
Tolosa
P
P
Armengol
A
A
Barnadas
A
A
Ariza
D000328:Adult; D000368:Aged; D001483:Base Sequence; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D003062:Codon; D011905:Genes, ras; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D017354:Point Mutation; D011379:Prognosis; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D016019:Survival Analysis
D003062:Codon; D009838:Oligodeoxyribonucleotides; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)