Codeletion of p15 and p16 in primary malignant mesothelioma

The p15 and p16 CDK4 inhibitor genes map within the chromosome band 9p21 region deleted frequently in malignant mesothelioma and other cancers. p16 has been implicated recently as a potential target of 9p21 deletions in mesothelioma, but the role of this gene is uncertain because deletions have been detected more often in established cell lines than in primary tumor specimens. We determined p15 and p16 copy number by fluorescence in situ hybridization with a P1 contig in 50 primary mesotheliomas. Codeletion of p15 and p16 was found in 72% of mesotheliomas, including all cases with spindle-cell components (n = 21) and total deletion of p15 and p16 was found in several mesotheliomas that lacked cytogenetic deletion of the chromosome 9 short arm. Point mutations were not found, however, in exon 2 of retained p15 and p16 alleles from seven mesotheliomas. These findings demonstrate that p15, p16 and/or a closely neighboring gene, are the targets of frequent chromosome 9p deletion in primary malignant mesothelioma.