Codeletion of p15 and p16 Genes in Primary Non-Small Cell Lung Carcinoma

Chromosome band 9p21 is deleted frequently in non-small cell lung carcinoma (NSCLC), and the pl5 and p16 cyclin-dependent kinase-4 inhibitor genes map within this deletion region. Recent studies demonstrated deletion of pl5 and pl6 in NSCLC metastases and cell lines, suggesting a role for these genes in NSCLC progression. We now report plS and pl6 copy number, as determined by fluorescence in situ hybridization with a PI contig, in 18 primary NSCLCs. Codeletion of p15 and pi6 was found in 15 of 18 NSCLCs, and 1 of the 3 tumors with normal plS and p16 copy number had a nonsense mutation in exon 2 of p16. We conclude that plS and pl6 are deleted and/or mutated in most primary NSCLCs. Two observations, however, support the involvement of at least one additional tumor suppressor gene on chromosome 9. These observations are: (a) the large size (>100 kb) of most NSCLC pl5/pl6 deletions; and (b) the absence of exon 2 mutations in most retained NSCLC p15 and p16 alleles.