Background Neuroblastoma is a childhood tumor derived from cellsof the neural crest, with a widely variable outcome. Differencesin the behavior and prognosis of the tumor suggest that neuroblastomacan be divided into several biologic subgroups. We evaluatedthe most frequent genetic abnormalities in neuroblastoma todetermine their prognostic value.
Methods We used Southern blot analysis to study the allelicloss of chromosomes 1p, 4p, 11q, and 14q, the duplication ofchromosome 17q, and the amplification of the N-myc oncogenein 89 neuroblastomas. We also determined the nuclear DNA contentof the tumor cells.
Results Allelic loss of chromosome 1p, N-myc amplification,and extra copies of chromosome 17q were significantly associatedwith unfavorable outcomes. In a multivariate analysis, lossof chromosome 1p was the most powerful prognostic factor. Itprovided strong prognostic information when it was includedin multivariate models containing the prognostic factors ofage and stage or serum ferritin level and stage. Among the patientswith stage I, II, or IVS disease, the mean (±SD) three-yearevent-free survival was 100 percent in those without allelicloss of chromosome 1p and 34±15 percent in those withsuch loss; the rates of three-year event-free survival amongthe patients with stage III and stage IV disease were 53±10percent and 0 percent, respectively.
Conclusions The loss of chromosome 1p is a strong prognosticfactor in patients with neuroblastoma, independently of ageand stage. It reliably identifies patients at high risk in stagesI, II, and IVS, which are otherwise clinically favorable. Moreintensive therapy may be considered in these patients. Patientsin stages III and IV with allelic loss of chromosome 1p havea very poor outlook, whereas those without such loss are atmoderate risk.
Source Information
From the Department of Pediatric Oncology and Hematology, Emma Kinderziekenhuis–Academic Medical Center (H.C., J.K., P.A.V.), and the Institute of Human Genetics, Academic Medical Center (H.C., P.S., R.S., A.W., R.V.), University of Amsterdam, Amsterdam; the Center of Pediatric Oncology of the Southeastern Netherlands, University of Nijmegen, Nijmegen (J.B.); and the Sophia Kinderziekenhuis, Erasmus University, Rotterdam (M.E.) — all in the Netherlands; and the Institute of Human Genetics, University Hospital of Ghent, Ghent, Belgium (G.L.).
Address reprint requests to Dr. Caron at the Department of Pediatric Oncology and Hematology, EKZ/AMC, P.O. Box 22700, 1100 DE Amsterdam, the Netherlands.
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