Prognostic impact of mutated K-ras gene in surgically resected non-small cell lung cancer patients

TY - JOUR

T1 - Prognostic impact of mutated K-ras gene in surgically resected non-small cell lung cancer patients

AU - Rosell, R

AU - Li, S

AU - Skacel, Z

AU - Mate, J L

AU - Maestre, J

AU - Canela, M

AU - Tolosa, E

AU - Armengol, P

AU - Barnadas, A

AU - Ariza, A

PY - 1993/9/1

Y1 - 1993/9/1

N2 - 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.

AB - 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.

KW - Adult

KW - Aged

KW - Base Sequence

KW - Carcinoma, Non-Small-Cell Lung

KW - Codon

KW - Genes, ras

KW - Humans

KW - Lung Neoplasms

KW - Male

KW - Middle Aged

KW - Molecular Sequence Data

KW - Oligodeoxyribonucleotides

KW - Point Mutation

KW - Prognosis

KW - Proto-Oncogene Proteins p21(ras)

KW - Survival Analysis

M3 - SCORING: Journal article

C2 - 8395679

VL - 8

SP - 2407

EP - 2412

JO - ONCOGENE

JF - ONCOGENE

SN - 0950-9232

IS - 9

ER -