Hematology and oncologyThe biologic basis for neuroblastoma heterogeneity and risk stratificationMaris, John MAuthor Information The Children’s Hospital of Philadelphia, Division of Oncology, and University of Pennsylvania School of Medicine and the Abramson Family Cancer Research Institute, Philadelphia, Pennsylvania, USA This work was supported in part by NIH grants R01-CA78545, R01-CA87847, R33-CA83220, P01-CA97323, The Abramson Family Cancer Research Institute, and the Children’s Oncology Group (U10-CA98543). Correspondence to John M. Maris, The Children’s Hospital of Philadelphia, Division of Oncology, ARC 902A, 324 South 34th Street, Philadelphia, PA 19104-4318, USA Tel: 215 590 5242; fax: 215 590 3770; e-mail: [email protected] Current Opinion in Pediatrics: February 2005 - Volume 17 - Issue 1 - p 7-13 doi: 10.1097/01.mop.0000150631.60571.89 Buy Metrics Abstract Purpose of review Neuroblastoma serves as the paradigm for the clinical utility of tumor-specific biologic data for prognostication. This review will describe the genetic and biologic basis for the diverse clinical phenotypes observed in neuroblastoma patients. It will also discuss the current approach to risk classification and how this may change in the future. Recent findings The biologic basis of neuroblastoma has come into clearer focus. PHOX2B is the first bona fide neuroblastoma predisposition gene identified, but is mutated in only a small subset of cases. Somatically acquired alterations at chromosome arms 3p and 11q are highly correlated with acquisition of metastases in the absence of MYCN amplification and may be useful as prognostic markers. The Children’s Oncology Group risk classification system has been validated, with current emphasis on further refinement such as reevaluation of the age cutoff used to stratify therapy, and incorporation of additional molecular genetic markers is being studied prospectively. High-throughput genome scale analyses of neuroblastomas are further clarifying the genetic basis of this heterogeneous disease. Summary Neuroblastoma remains a significant challenge as high-risk patients are treated with intensive multimodal therapies but cure rates remain suboptimal. There is remarkable heterogeneity observed in tumor phenotype, ranging from spontaneous regression to relentless progression. There are literally dozens of clinical and biologic markers that have been proposed as being predictive of disease outcome, but large clinical correlative studies are sharpening the focus of which markers can be used by the clinician to optimize therapy for an individual patient. © 2005 Lippincott Williams & Wilkins, Inc.