Nras and Kras mutation in Japanese lung cancer patients: Genotyping analysis using LightCycler.
Activating mutations of Ras gene families have been found in a variety of human malignancies, including lung cancer, suggesting their dominant role in tumorigenesis. Many studies have showed that the Kras gene is activated by point mutations in approximately 15-20% of non-small cell lung cancers (NSCLCs), however, there are only a few reports on Nras mutations in NSCLC. We have genotyped Nras mutation status (n=195) and Kras mutation status (n=190) in surgically treated lung adenocarcinoma cases. The presence or absence of Nras and Kras mutations was analyzed by real-time quantitative polymerase chain reaction (PCR) with mutation-specific sensor and anchor probes. EGFR mutation status at kinase domain has already been reported. Nras mutation was found in 1 of 195 patients. This mutation was a G-to-T transversion, involving the substitution of the normal glycine (GGT) with cystein (TGT) and thought to be a somatic mutation. The patient was male and a smoker. Kras mutant patients (11.1%; 21/190) had a significantly worse prognosis than wild-type patients (p=0.0013). Eighty-two EGFR mutations at kinase domain had exclusively Nras or Kras mutations. Although Nras gene mutation might be one of the mechanisms of oncogenesis of lung adenocarcinoma, this was a very rare event. Further studies are needed to confirm the mechanisms of Nras mutations for the sensitivity of molecular target therapy for lung cancer.
Sasaki
Hidefumi
H
Department of Surgery II, Nagoya City University Medical School, Nagoya 467-8601, Japan. hisasaki@med.nagoya-cu.ac.jp
Okuda
Katsuhiro
K
Kawano
Osamu
O
Endo
Katsuhiko
K
Yukiue
Haruhiro
H
Yokoyama
Tomoki
T
Yano
Motoki
M
Fujii
Yoshitaka
Y
D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D000368:Aged; D019943:Amino Acid Substitution; D005260:Female; D011905:Genes, ras; D005821:Genetic Techniques; D005838:Genotype; D006801:Humans; D007564:Japan; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D015996:Survival Rate; D018631:ras Proteins / Q000235:genetics*
C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins