The pattern of K-ras mutation in pulmonary adenocarcinoma defines a new pathway of tumour development in the human lung.

Codon 12 of the K-ras oncogene was screened for mutations in 65 surgically-resected primary pulmonary adenocarcinomas and in 32 tissue foci of alveolar atypical hyperplasia (AAH) by a polymerase chain reaction (PCR)-based method. Mutations in either position 1 or position 2 of codon 12 were detected in 16 tumours (25 per cent). When analysed by site of origin, mutations were seen in 9/26 (35 per cent) parenchymal and in 0/12 bronchial adenocarcinomas (P < 0-02), K-ras mutations were seen in five AAH lesions from four patients. DNA sequencing showed that the great majority of mutations in both adenocarcinomas and AAH were G-T transversions. These findings provide support for the classification of pulmonary adenocarcinomas into bronchial and parenchymal subtypes and also provide molecular evidence to support the importance of AAH in the development of parenchymal cancers.