COINCIDENTAL ALTERATIONS OF P16(INK4A CDKN2) AND OTHER GENES IN HUMANLUNG-CANCER CELL-LINES/

Cyclin-dependent kinase (CDK) inhibitor genes have recently been propo sed as new tumor suppressor genes. To define the possible participatio n of CDK inhibitor genes in lung carcinogenesis, we investigated the a lterations of p15(INK4B), p16(INK4A), p21(Waf1), and p27(Kip1) genes i n 34 human lung cancer cell lines using the polymerase chain reaction- single strand conformation polymorphism (PCR-SSCP), direct sequencing, and southern dot blot methods. Among the four CDK inhibitor genes, al terations of only the p16(INK4A) gene were found in 8 out of 34 (24%) cell lines, and all eight cell lines having a p16(INK4A) gene alterati on had an alteration of either the K-ras or p53 gene. Conversely, p16( INK4A) gene alterations were found in none of the 3 cell lines having Rb gene alterations and none of the 3 cell lines having amplification of the N-myc gene. Polymorphism was found in both p21(Waf1) and p27(Ki p1) genes, but no association was found between the polymorphism and a lterations of other genes. These results suggest that p16(INK4A) gene alterations may play a certain role for lung carcinogenesis in co-oper ation with either K- ras orp53 gene alterations.