Association of MYCN copy number with clinical features, tumor biology, and outcomes in neuroblastoma: A report from the Children's Oncology Group

BACKGROUND High‐level MYCN amplification (MNA) is associated with poor outcome and unfavorable clinical and biological features in patients with neuroblastoma. To the authors' knowledge, less is known regarding these associations in patients with low‐level MYCN copy number increases. METHODS In this retrospective study, the authors classified patients has having tumors with MYCN wild‐type tumors, MYCN gain (2‐4‐fold increase in MYCN signal compared with the reference probe), or MNA (>4‐fold increase). Tests of trend were used to investigate ordered associations between MYCN copy number category and features of interest. Log‐rank tests and Cox models compared event‐free survival and overall survival by subgroup. RESULTS Among 4672 patients, 3694 (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 percentage 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