Fig. 5

Schematic representation of the Genome Instability Progressive model of metastatic Neuroblastoma. The GIP model suggests a common ancestor for metastatic “stage 4S and 4 NBs”, showing that a deregulated endomitosis, chromosome mis-segregation and abnormal mitosis in the neural crest progenitors lead to aneuploid cells. This cell may generate “Stage 4S cell clone”, characterized mainly by numerical aberrations. However the clone maintains the capacity to active cell death or differentiation programs as mechanism to escape the catastrophic mitosis. Conversely the deregulated neural crest cells (NNC) may also generate “Stage 4 cell clone” with high genomic instability resulting in complex chromosome rearrangements. Finally, in the GIP model chromosomal deletions are late events, resulting in increasing of genomic chaos and progressive increase of genomic instability, with consequent tumor progression