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.

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