K-RAS POINT MUTATION OCCURS IN THE EARLY-STAGE OF CARCINOGENESIS IN LUNG-CANCER

In order to determine the topographical distribution of the K-ras codo n 12 mutations in carcinoma and preneoplastic lesions of the lung, sel ective ultraviolet radiation fractionation, as well as microdissection followed by polymerase chain reaction-restriction fragment length pol ymorphism (PCR-RELP), was performed. Fourteen of 61 samples amplified (23.0%) had a mutation in the K-ras codon 12. Of 41 adenocarcinoma, 12 samples (29.3%) had a mutation, whereas none of the squamous cell car cinomas had a mutation, One of six large-cell carcinomas, one of three carcinoid rumours and none of three other carcinomas had a mutation. Direct sequencing revealed that K-ras codon 12 of six samples were TGT (Cys), five samples were GTT (Val), two samples were GCT (Ala) and on e sample was TTT (Phe). A total of 113 lesions of 13 cases covered by dot were amplified after UV radiation. All of 74 carcinoma lesions had the mutation, and intratumour heterogeneity was not observed. Of 39 n on-malignant lesions, one type II cell hyperplasia had the mutation, w hich suggests that the K-ras mutation occurs in the early stage of car cinogenesis. The lack of intratumour heterogeneity supports the hypoth esis.