Turkish Journal of Medical Sciences




Lung cancer is the major cancer in Turkey; 45% of the deaths due to cancer in Turkish males are from lung cancer. There are 8 histopathological types of lung cancer, and most types have several genomic/genetic alterations, including amplification of oncogenes. The current study evaluated the ras oncogene in human lung cancers from Turkish patients. Thirty-six normal and pathological lung tissue specimens were obtained from patients with chest disease during surgery, frozen at -86°C, and processed within 2-3 months. Mutations in K-ras, codon 12 were analyzed using a series of DNA purification proceedures, polymerase chain reaction amplification, and dot-blotting techniques. Fifteen of the 21 cancer tissues had K-ras mutations. None of the 11 normal lung tissues nor any of the 4 other pathological tissues showed K-ras mutations. Seven of 11 epidermoid carcinomas, 3 of 3 adenocarcinomas, 2 of 3 bronchial carcinomas, 1 of 2 mesotheliomas, 1 of 1 metastatic anaplastic carcinoma, and 1 of 1 rabdomyosarcoma showed point mutations in codon 12, base pairs n 34 and/or 35. Base pair n 34 was mutated G->A in 11 samples and G->T in 4 samples, while base pair n 35 was mutated G->T in 8 samples. There were 3 triple and 3 double mutations in this group of cancers. Because G->A and G->T mutations are considered to be related to specific chemicals in cigarette smoke, and because 13 of the 15 cancer patients, who had K-ras mutations, were heavy smokers, the results from this study directly support, at the molecular level, close linkages between cigarette smoking and carcinogenic mutations in human lung tissues.

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