Gian Paolo Tonini

By Gian Paolo Tonini

It is widely accepted that neuroblastoma origin from Neural Crest Cells (NCC). NCC is a group of embryonic cells located in proximity to neural tube. During the embryonic development they migrate to generate the ganglia of sympathetic nervous system and the adrenal medulla. More than 50% of neuroblastoma masses are detected in the abdomen but the phases of tumorigenesis during the embryonic life are still unknown. Neuroblastoma cells show numerous copy number aberrations (CNAs), both numerical and structural. Several non-random CNAs are detected in clinical stage 4 and associated with tumor aggressiveness. On the contrary, neuroblastoma cells of infants or young patients have several numerical CNAs that are associated with a favorable outcome. MYCN oncogene amplification was one of the first genetic abnormalities observed in neuroblastoma and was found correlated to tumor aggressiveness. About 1% of all neuroblastoma show a hereditable fashion. Nowadays, the ALK gene has been discovered as predisposition gene for neuroblastoma. Moreover, thank to the genome-wide association studies, BARD1, LMO1 and LIN28 genes have been found linked to neuroblastoma predisposition. The two-step and multistep models are not satisfied the genesis of this tumor making the study of neuroblastoma tumorigenesis mandatory. Recently, the role of chromosome instability (CIN) became prominent to explain the neuroblastoma development. Indeed, the chromothripsis was observed in neuroblastoma cells of clinical stage 4, supporting the high genomic instability of these cells. The role of CIN in neuroblastoma is still unclear, but several experimental data suggest that CIN has a pivotal part in the genesis of neuroblastoma.

Part of the book: Neuroblastoma