The p16 and p18 tumor suppressor genes in neuroblastoma: implications for drug resistance

The cyclin dependent kinase inhibitors p16 and p18 were investigated in neuroblastoma. Only one of 19 neuroblastoma cell lines, an adriamycin-resistant variant, and none of 5 primary neuroblastoma, was deleted for p16 while its parental drug sensitive cell line is p16 intact. The region of deletion minimally extended centromeric to include p15, and telomeric to interferon-beta. This is the first report of a p16 gene alteration in neuroblastoma. No p16 gene hypermethylation or mutations were found. No homozygous deletions of p18 in these samples were found, although several instances of loss of heterozygosity are suspected. No p18 point mutations were detected. We conclude that (1) neither p16 nor p18 are likely involved in the pathogenesis of neuroblastoma; and (2) the role of p16, or another 9p21 gene, in the development of drug resistance warrants further investigation.