Taken together, our findings suggested that CAI2 contributes to the paradoxical overexpression of p16 in neuroblastoma, where CAI2 may offer a useful biomarker of high-risk disease.
Impact of E27X, a novel CDKN2A germ line mutation, on p16 and p14ARF expression in Italian melanoma families displaying pancreatic cancer and neuroblastoma.
In contrast to the absence of expression of the known tumor suppressor CDKN2A (also known as p16 and INK4A) in a wide variety of tumor types we have found in previous studies that CDKN2A protein is paradoxically highly expressed in many advanced stage neuroblastomas and unrelated to RB1 status.
No mutations to the p16-binding site of CDK4 and CDK6 nor any mutations to the coding region of p16 itself were identified in neuroblastoma cell lines.
Differentiation between benign and malignant tumors of the adrenal cortex was attempted by microdissection of nine cases of adrenal cortical hyperplasia, 10 cortical adenomas, and 18 adrenal cortical carcinomas with subsequent polymerase chain reaction (PCR) amplification for loss of heterozygosity (LOH) of five microsatellites of putative tumor suppressor gene loci: p53 gene (17p), the neuroblastoma candidate gene (1p), the p16 gene (9p), the von Hippel Lindau gene (3p), and the retinoblastoma gene (13q).
We conclude that the common pattern of p16 inactivation by homozygous deletion or mutation does not seem to be relevant to the development of neuroblastomas.
This result suggests the presence of at least one other tumor suppressor gene at 9p21, apart from the p16 and p15 genes, which may be of importance to the development of neuroblastoma.
Because the commonly deleted regions at 9p21 includes the p16 (CDKN2A) gene, the status of the p16 gene was further examined in 80 fresh tumors and 19 cell lines of neuroblastoma.
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.