Molecular pathogenesis of peripheral neuroblastic tumors

Abstract

Neuroblastoma (NB) is an embryonal cancer of the sympathetic nervous system observed in early childhood, characterized by a broad spectrum of clinical behaviors, ranging from spontaneous regression to fatal outcome despite aggressive therapies. NB accounts for 8-10% of pediatric cancers and 15% of the deaths attributable to malignant conditions in children. Interestingly, NB may occur in various contexts, being mostly sporadic but also familial or syndromic. This review focuses on recent advances in the identification of the genes and mechanisms implicated in NB pathogenesis. Although the extensive characterization of the genomic aberrations recurrently observed in sporadic NBs provides important insights into the understanding of the clinical heterogeneity of this neoplasm, analysis of familial and syndromic cases also unravels essential clues on the genetic bases of NB. Recently, the ALK gene emerged as an important NB gene, being implicated both in sporadic and familial cases. The identification of gene expression signatures associated with patient's outcome points out the potential of using gene expression profiling to improve clinical management of patients suffering from NB. Finally, based on recent observations integrating genomic analyses, biological data and clinical information, we discuss possible evolution/progression schemes in NB.