Neuroblastoma: a multiple biological disease

Neuroblastoma (NB) is a paediatric tumour showing an appreciable variability in clinical evolution. Localised tumours (especially stage 1) can be mildly treated with good success while metastatic tumours (stage 4) are highly aggressive. This suggests a great biological diversity. In fact, molecular and genetic studies have revealed distinct abnormalities in localised and non-localised tumours. Loss of heterozygosity for the short arm of chromosome 1, 1p deletion, and MYCN amplification are present in stages 3 and 4 but rarely in stages 1 and 2. Metastatic stage 4S in infants is peculiar and does not show the same genetic and molecular abnormalities found in advanced metastatic tumours. Considering the biological alterations associated with NB, it would appear that advanced stage NB conforms to the multistep model of tumour development while stage 4S can be divided into two groups: one arising from a lack of cellular differentiation and the other as a consequence of an additional 'one hit' mutation.