K-RAS ONCOGENE ACTIVATION IN ATYPICAL ALVEOLAR HYPERPLASIAS OF THE HUMAN LUNG

Atypical alveolar hyperplasia (AAH) is a potential precursor lesion fr om which lung adenocarcinomas arise and may be a good target for study ing the early events of lung tumorigenesis, A common genetic alteratio n in lung adenocarcinomas is mutational activation of K-rns, To determ ine the timing of K-ras activation, we evaluated formalin-fixed and pa raffin-embedded tissue samples of 41 AAHs and their paired lung neopla sms from 28 patients for codon 12 point mutations of the K-ras oncogen e, K-ras codon 12 mutations were detected using PCR followed by allele -specific oligonucleotide hybridization, Mutations were found in 16 (3 9%) of the 41 AAHs, 8 (42%) of the 18 adenocarcinomas, and none (0%) o f the 5 lung neoplasms that were not adenocarcinomas. Of the 18 patien ts with both an AAH and a synchronous lung adenocarcinoma, 6 had K-ras mutations in the adenocarcinoma but not in the AAH, 6 had mutations i n the AAH but not in the adenocarcinoma, 4 did not harbor mutations in either the AAH or the adenocarcinoma, and 2 had mutations in both the ir AAH and their synchronous adenocarcinoma, In just 1 of the 18 patie nts was the same K-ras mutation present in the AAHs and adenocarcinoma of the patient, The detection of independent activating point mutatio ns in a cancer-causing gene points to the neoplastic nature of AAH and suggests that glandular neoplasms of the lung arise from a background of field cancerization.