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i I I I I I I I I I I I I I I I AMPLIFICATION AND POINT MUTATION OF THE HA-RAS ONCOGENE IN LUNG CANCER Chen Jia-kun, He Ling, Wu Zhong-liang and Du Ying-xiu Institute for Chemical Carcinogenesis, Guangzhou Medical College, Guangzhou, China In order to determine the biological role of the Ha-ras oncogene in the pathogenesis of lung cancer, 24 primary lung cancer cases and 5 adjacent tissues were analyzed for Ha-ras oncogene amplification by Southern blot hybridization and 27 primary lung cancer cases, 3 adjacent tissues and 5 normal lung tissues were analyzed for point mutation of this gene by polymerase chain reaction (PCR) and restriction fragment length polymorphism (PCR-RFLP). The results showed that amplification of the Ha-ras gene occurred in 22% (2/9) of adenocarcinoma cases and in 80% (8/10) of squamous cell carcinoma cases. However, in all five tumor adjacent tissues, Ha-ras gene amplification was not observed. By PCR-RFLP analysis, 9 of 27 (33%) lung cancer cases showed point mutations of the Ha- ras gene: 67% (6/9) of adenocarcinoma cases and 20% (3/15) of squamous cell carcinoma cases. No point mutations of the Ha-ras gene were observed in any of the small cell lung cancer cases, adjacent tissues and normal lung tissues. These results suggest that amplification and point mutation of the Ha-ras gene may play an important role in the development of lung cancer. Amplification of the Ha-ras oncogene was more apparent in squamous cell carcinoma than in adenocarcinoma, whereas the point mutation of the Ha-ras gene was more frequent in adenocarcinoma than in squamous cell carcinoma. N O ~ -4 W W O C) I