title: Molecular biology of neuroblastoma.
abstract: PURPOSE AND RESULTS: Neuroblastoma, the most common solid extracranial neoplasm in children, is remarkable for its clinical heterogeneity. Complex patterns of genetic abnormalities interact to determine the clinical phenotype. The molecular biology of neuroblastoma is characterized by somatically acquired genetic events that lead to gene overexpression (oncogenes), gene inactivation (tumor suppressor genes), or alterations in gene expression. Amplification of the MYCN proto-oncogene 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 neuroblastoma, 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 neuroblastoma, 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. Alterations in the expression of the neurotrophins and their receptors correlate with clinical behavior and may reflect the degree of neuroblastic differentiation 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 well-defined subset of patients.
  
  
  CONCLUSIONS
  The molecular biology of neuroblastoma has led to a combined clinical and biologic risk stratification. Future advances may lead to more specific treatment strategies for children with neuroblastoma.
authors.affiliation: Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA 19104-4318, USA. maris@email.chop.edu
authors.forename: J M
authors.initials: JM
authors.lastname: Maris
authors.forename: K K
authors.initials: KK
authors.lastname: Matthay
mesh_terms: D002648:Child; D002869:Chromosome Aberrations; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor / Q000235:genetics; D016259:Genes, myc / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D008957:Models, Genetic; D009447:Neuroblastoma / Q000235:genetics*; D000090063:Proto-Oncogene Mas