P16 CDKN2 GENE AND P53 GENE ALTERATIONS IN JAPANESE NONSMOKING FEMALELUNG ADENOCARCINOMA/

Primary lung adenocarcinomas in non-smoking females are increasing in the USA and Japan. Environmental factors such as passive smoking, asbe stos, domestic radon, and hormonal effects have been implicated, but t he etiology is still uncertain. We therefore analyzed point mutations of p16 gene, a newly characterized tumor suppressor gene, and compared the results with alterations of p53 gene in 28 primary lung adenocarc inomas in non-smoking Japanese females. There were no cases with somat ic point mutation of p16 gene, except for one case with two germline m utations (silent mutations). In contrast, six out of 16 informative ca ses showed loss of heterozygosity of p53 gene using a TP53 microsatell ite marker and 19 out of 28 cases showed expression of oncoprotein usi ng DO-7 immunohistochemistry. These findings suggest that p16 gene alt eration is a rare event in primary lung adenocarcinomas in Japanese no n smoking females, compared with alterations of the p53 gene.