T. Urban et al., Detection of codon 12 K-ras mutations in non-neoplastic mucosa from bronchial carina in patients with lung adenocarcinomas, BR J CANC, 82(2), 2000, pp. 412-417
K-ras activation by point mutation in codon 12 has been reported in lung ad
enocarcinomas in various models of experimental lung tumours induced by che
mical carcinogens. The hypothesis of the presence of cells containing K-ras
mutation in non neoplastic bronchial carina;the main site of impaction of
airborne contaminants, was investigated by evaluating concurrent lung tumou
r and non-neoplastic proximal bronchial carinae from 19 patients with lung
adenocarcinomas. The restriction fragment length polymorphism enriched PCR
method used can detect one mutant allele among 10(3) normal alleles. a muta
tion was detected in 42% of lung adenocarcinoma samples. No mutation was de
tected in either tumour or bronchial carinae in nine patients (47%). K-ras
mutation was detected in the! lung tumour but not in bronchial carinae in f
our patients (21%), in both the lung tumour and bronchial carinae in four o
ther patients (21%). In two patients (11%), K-ras mutation was detected in
at least one bronchial carina; but not in the lung tumour. Mutations of cod
on 12, confirmed by sequencing analysis of ten samples, were G to T transve
rsion, mostly TGT and GTT in bronchial carinae and lung tumours. Our data s
how that activated K-ras by point mutation can be present in non-neoplastic
bronchial carina mucosa even when no mutation is detected in tumour sample
s. (C) 2000 Cancer Research Campaign.