INTRAGENIC MUTATIONS OF THE P16(INK4), P15(INK4B) AND P18 GENES IN PRIMARY NON-SMALL-CELL LUNG CANCERS

The p15(INK4B), p(16INK4) and p18 genes are members of the gene family coding for inhibitors of cyclin-dependent kinases 4 and 6. p15(INK4B) and p16(INK4) are located at 9p21, a chromosomal region frequently de leted in many human neoplasms. To examine the role of these 3 genes in lung carcinogenesis, somatic mutations within the genes were analyzed by single-strand conformation polymorphism and DNA sequencing in 71 n on-small-cell lung cancer (NSCLC) samples. Six somatic mutations in th e p16(INK4) gene and 3 cases with a polymorphic allele were observed. Loss of heterozygosity in the p18 gene was found in I sample. We did n ot find any intragenic mutations in the p15(INK4B) Or p18 genes. We co nclude that p16(INK4) mutations play a role in the formation of some N SCLCs, whereas the involvement of p15(INK4B) and p18 is uncommon. (C) 1996 Wiley-Liss, Inc.