Mutations in the K-ras gene are frequently identified in lung tumors. Although K-ras mutations are implicated in the development of lung cancer, their significance and the timing of their occurrence in lung carcinogenesis remain poorly understood. Several studies applied various methods to characterize K-ras mutations in lung tissues or cell samples taken at different stages of tumorigenesis. We used a laser capture microdissection microscope to sample cells from histopathologically-differing areas of paraffin-embedded lung tissue sections for mutation analysis. Our data showed the presence of K-ras mutations in normal-appearing tissues surrounding lung tumors in some cases of lung cancer. Some of these cases contained an identical mutation in both the tumor and normal appearing tissues, while other cases showed mutations in normal-appearing tissue different from those found in the matched tumor. These results suggest that K-ras mutations may represent early events in some cases of lung cancer and may provide a useful exposure marker for lung carcinogens.

Key words: carcinogenesis, K-Ras mutation, lung cancer, lung tumor.