Whole Chromosome Alterations Predict Survival in High-Risk Neuroblastoma without MYCN Amplification

Purpose: Patients with stage IV neuroblastoma over the age of 500 days without MYCN amplification have a survival rate of <30% and there are currently no reliable means of predicting which of these patients will survive or succumb to the disease. The goal of this study is to develop a DNA copy number–based prognostic profile for these patients. Experimental Design: We have used comparative genomic hybridization to identify genome copy number changes that can predict outcome in patients with stage IV neuroblastoma without MYCN amplification. Results: A strong correlation of patient survival with the presence of whole chromosome changes (WCC ≥2) was observed, even in the group of patients older than 500 days at time of diagnosis. This novel prognostic marker showed a significant dependence on the date of diagnosis; patients with WCC ≥2 diagnosed after 1998 had a significantly higher probability of survival compared with those diagnosed earlier. At the same time, no such time dependence was found among the samples with WCC <2, suggesting that medical progress patients in recent years has particularly benefited those patients with a stage IV non–MYCN-amplified disease if WCC ≥2 were present. Conclusions: In this pilot study, we present a novel prognostic marker for survival of high-risk neuroblastoma patients over the age of 500 days without MYCN amplification and diagnosed after 1998. Further validation study is required to establish this risk stratification for these patients.