Background High-level MYCN amplification (MNA) is associated with poor outcome and unfavorable clinical and biological features in neuroblastoma. Less is known about these associations in patients with low-level MYCN copy number increases. Methods In this retrospective study, we defined patients as having tumors with MYCN wild-type, MYCN gain (2–4 fold increase in MYCN signal compared to reference probe), or MNA (>4 fold increase). We used tests of trend to investigate ordered associations between MYCN copy number category and features of interest. Log-rank tests and Cox models compared event-free (EFS) and overall survival (OS) by subgroup. Results Among 4,672 patients, 3,694 (79.1%) had MYCN wild-type tumors, 133 (2.8%) had MYCN gain, and 845 (18.1%) had MNA. For each clinical/biological feature, the proportion of patients with an unfavorable feature was lowest in the MYCN wild-type category, intermediate in the MYCN gain category, and highest in the MNA category (p<0.0001), except for 11q aberration where the highest rates were in the MYCN gain category. Patients with MYCN gain had inferior EFS and OS compared to wild-type. Among patients with high-risk disease, MYCN gain was associated with the lowest response rate following chemotherapy. Patients with non-stage 4 disease and patients with non-high risk disease with MYCN gain had significantly increased risk for death, a finding confirmed on multivariable testing. Conclusions Increasing MYCN copy number is associated with an increasingly higher rate of unfavorable clinical/biological features, with 11q aberration an exception. Patients with MYCN gain have inferior outcomes, especially in otherwise more favorable groups.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.