Molecular biology of neuroblastoma

Purpose and Results: Neuroblastoma,the most common solid extracranial neopl asm in children, is remarkable for its clinical heterogeneity. Complex patt erns of genetic abnormalities interact to determine the clinical phenotype, The molecular biology of neuroblastoma is characterized by somatically acq uired genetic events that lead to gene overexpression (oncogenes), gene ina ctivation (tumor suppressor genes), or alterations in gene expression. Ampl ification of the MYCN protooncogene occurs in 20% to 25% of neuroblastomas and is a reliable marker of aggressive clinical behavior. No other oncogene has been shown to be consistently mutated or overexpressed in neuroblastom a, although unbalanced translocations resulting in gain of genetic material from chromosome bands 17q23-qter have been identified in more than 50% of primary tumors. Some children have an inherited predisposition to develop n euroblastoma, but a familial neuroblastoma susceptibility gene has not yet been localized. Consistent areas of chromosomal loss, including chromosome band 1p36 in 30% to 35% of primary tumors, 11q23 in 44%, and 14q23-qter in 22%, may identify the location of neuroblastoma suppressor genes. Alteratio ns in the expression of the neurotrophins and their receptors correlate wit h clinical behavior and may reflect the degree of neuroblastic differentiat ion before malignant transformation. Alterations in the expression of genes that regulate apoptosis also correlate with neuroblastoma behavior and may help to explain the phenomenon of spontaneous regression observed in a wel l-defined subset of patients. Conclusion: The molecular biology of neuroblastoma has led ta a combined cl inical and biologic risk stratification, Future advances may lead to more s pecific treatment strategies for children with neuroblastoma. (C) 1999 by A merican Society of Clinical Oncology.