High frequency of K-ras mutations in normal appearing lung tissues and sputum of patients with lung cancer.
To evaluate the possible use of mutant ras as a biomarker for lung cancer, we have analyzed "normal appearing" lung tissue, lung tumor, lung metastases and sputum samples from patients with non-small cell lung cancer (NSCLC). As a control, we used lung tissue and sputum samples from patients without oncological diseases or lung disorders. Our analyses were performed with the aid of enriched PCR (EPCR), a method which enables detection of ras mutation even if present at low incidence. EPCR identified K-ras codon 12 mutations in 10% of lung tissues obtained from patients with no lung diseases, whereas the same mutation was detected in 60% of samples of normal appearing lung tissues obtained from patients with NSCLC, 62% of NSCLC tumors and 80% of metastases. Analysis of sputum samples of patients with NSCLC identified 47% to harbor mutant ras allele, whereas 12.5% of controls diagnosed with non-oncological lung diseases carried this mutation. Most of these mutations were detected with the aid of EPCR only, indicating that a minority of cells in a given sample harbor this mutation. The ability to detect K-ras codon 12 mutation in 60% of lung tissue samples and in 47% of sputum samples taken from patients with lung cancer (as compared with 10% and 12.5% of respective controls) points to the potential use of ras mutation as a biomarker for exposure and possible identification of patients who may be at higher risk of developing lung cancer.
Yakubovskaya
M S
MS
Institute of Carcinogenesis, Russian Academy of Medical Sciences, Moscow, Russian Federation.
Spiegelman
V
V
Luo
F C
FC
Malaev
S
S
Salnev
A
A
Zborovskaya
I
I
Gasparyan
A
A
Polotsky
B
B
Machaladze
Z
Z
Trachtenberg
A C
AC
D000368:Aged; D003062:Codon / Q000235:genetics; D005260:Female; D006801:Humans; D008168:Lung / Q000378:metabolism*; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015689:Oncogene Protein p21(ras) / Q000235:genetics*; D013183:Sputum / Q000378:metabolism*
D003062:Codon; D015689:Oncogene Protein p21(ras)