Amplification of CDK4 and MDM2: a detailed study of a high-risk neuroblastoma subgroup.

ABSTRACT: In neuroblastoma, MYCN amplification and 11q-deletion are important, although incomplete, markers of high-risk disease. It is therefore relevant to characterize additional alterations that can function as prognostic and/or predictive markers. Using SNP-microarrays, a group of neuroblastoma patients showing amplification of one or multiple 12q loci was identified. Two loci containing CDK4 and MDM2 were commonly co-amplified, although amplification of either locus in the absence of the other was observed. Pharmacological inhibition of CDK4/6 with ribociclib or abemaciclib decreased proliferation in a broad set of neuroblastoma cell lines, including CDK4/MDM2-amplified, whereas MDM2 inhibition by Nutlin-3a was only effective in p53^wild-type cells. Combined CDK4/MDM2 targeting had a

SUBMITTER: Martinez-Monleon A 

PROVIDER: S-EPMC9300649 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature