High frequency of K‐ras mutations in normal appearing lung tissues and sputum of patients with lung cancer

Abstract

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.

Allelic imbalance and instability of microsatellite loci on chromosome 1p in human non-small-cell lung cancer

“…Previously, we detected a mutant KRAS gene (codon 12) in case no. 6 out of 30 analysed (Yakubovskaya et al, 1995). The findings indicate high genetic instability of this tumour.…”

Clinical Application of Automatic Gene Chip Analyzer (WEnCA-Chipball) for Mutant Kras Detection in Peripheral Circulating Cancer Cells of Cancer Patients

“…As early as 1989, Slebos et al have identified that the KRAS mutation status can be used for lung cancer detection or prognosis prediction (Slebos & Rodenhuis, 1989). In 1995, Yakubovskaya et al detected 12 different KRAS mutations in nearly 60% of tissue specimens of non-small cell lung cancer (NSCLC) patients (Yakubovskaya et al, 1995). As for pancreatic, stomach and breast cancers, there have been a number of studies reporting KRAS mutations (Smit et al, 1988;Gocke et al, 1997;Deramaudt & Rustgi, 2005;Carstens et al, 1988;Lee et al, 2003;Shen et al, 2008).…”

Early detection of squamous cell lung cancer in sputum by a panel of microRNA markers

“…[6][7][8] Therefore, molecular study of sputum has been suggested to be more sensitive than cytology in diagnosis of lung cancer. [6][7][8][9][10] For instance, hypermethylation of p16 gene was found in sputum collected from patients with lung squamous cell carcinomas, 5-35 months before sputum cytological and clinical diagnoses. 11 MicroRNAs (miRNAs) are a newly discovered class of small noncoding RNAs that have critical roles in a wide spectrum of biologic and pathologic processes.…”