Modelling neuroblastoma using human trunk neural crest cells

Neuroblastoma (NB) is a childhood cancer which contributes to approximately 15 percent of all pediatric cancer related deaths. NB is a heterogeneous disease; non-high risk NB patients show good prognosis but high-risk NB patients often do not respond to multimodal therapy with frequent relapse. This suggests we need better understanding of the disease mechanism for effective treatment strategies for high-risk NB patients.  MYCN amplification is one of the most frequent genetic aberrations observed in neuroblastoma and MYCN amplification is often associated with aggressive disease. Neuroblastoma is thought to develop because of improper differentiation of the trunk neural crest cells (tNCCs) which normally contribute to the sympathetic nervous system. The role of MYCN in NB tumorigenesis has been studied using mouse model systems, but important differences exist between mouse and human NCCs which demands novel model systems. MYCN amplified cell lines are one such model system which has been explored to understand MYCN functions in these cells. However, in these cell line models we lack the information of what are early events which prevent differentiation of the tNCCs which leads to NB tumor formation.  In our laboratory, we have developed human tNCCs in vitro by differentiating human ES cells, and using these tNCCs we are trying to model the MYCN mediated tumorigenesis. Using transcriptomics and epigenomics based approaches we aim to decipher the early events during MYCN mediated oncogenesis. We hope our study of MYCN mediated oncogenesis using the human tNCC model will provide a better understanding of NB disease, which can be exploited further for therapeutic intervention.