The MYCN oncogene plays a role in neuroblastoma
tumorigenesis, defining an aggressive subset of tumors. MYCN was found to be
amplified in 20-25% of NB cases, conferring a poor prognosis 5. MYC proteins
transform primary cells, and can convert established cell lines in
tumourigenicity 7. Transgenic mouse models have been used to show that
deregulated MYCN expression targeted to the neural crest is necessary to drive
tumorgenesis with elevated penetrance abcd. This transcription factor can
activate and repress genetic targets through direct DNA binding and indirect
protein-protein interaction mechanisms cleo. MYCN and c-MYC have been found
to be anti-p53, pro-EMT functions, and proliferative functions andrex. MYCN
is transiently expressed, during normal embryogenesis and neural crest
development, in the ventral-lateral migrating crest cells that later become
sympathetic ganglia. Therefore high levels of MYCN can be found in a subset of
poorly differentiated aggressive neuroblastomas duck. MYCN has been targeted
in clinical approaches, however many high-risk cases have minimal MYCN
expression, implying additional mechanisms for tumorigenesis independent of
MYCN deregulation oui.

Patients with MYCN amplification are treated with multimodality treatment
strategy.  Strong association with
prognosis allows those with favorable cytogenetics to be exposed to lower
treatment toxicity levels. This results in fewer later effects. Novel
biological therapeutics targeting these pathways may restore sensitivity to the
inherent death priming function of deregulated n-MYC 8, and to traditional
anti-neoplastic agents.

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GWAS’s have shown significant association
between clinically aggressive NB’s and common single nucleotide polymorphisms.

This suggests that these variants are associated with a susceptibility to NB,
especially to metastatic disease with MYCN amplification, and a high
probability of relapse u.