Coincidental alterations of p16INK4A/CDKN2 and other genes in human lung cancer cell lines

Cyclin-dependent kinase (CDK) inhibitor genes have recently been proposed as new tumor suppressor genes. To define the possible participation of CDK inhibitor genes in lung carcinogenesis, we investigated the alterations of p15(INK4B), p16(INK4A), p21(Waf1), and p27(Kip1) genes in 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, alterations 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 alteration 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(Kip1) genes, but no association was found between the polymorphism and alterations of other genes. These results suggest that p16(INK4A) gene alterations may play a certain role for lung carcinogenesis in co-operation with either K- ras orp53 gene alterations.