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

Authors' Affiliations: ¹ Oncogenomics Section, Pediatric Oncology Branch, Advanced Technology Center, National Cancer Institute, Gaithersburg, Maryland; ² Cancer Genetics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland; and ³ Advanced Biomedical Computing Center, Science Applications International Corporation-Frederick, Inc., National Cancer Institute-Frederick, Frederick, Maryland

Requests for reprints: Javed Khan, National Cancer Institute, 8717 Grovemont Circle, Room 134E, Bethesda, MD 20892-4605. Phone: 301-435-2937; Fax: 301-480-0314; E-mail: khanjav{at}mail.nih.gov.

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.