Neuroblastoma (NB) is a childhood cancer which thought to derive because of improper differentiation of trunk neural crest cells (tNCCs) which form the sympatho-adrenergic lineage. Crest cells are versatile in nature as they can give rise to many different cell types but are less studied because of lack of proper model system. MYCN is frequently amplified in high risk NBs but it is not properly understood how MYCN affects the gene expression in tNCCs. The current proposal aim to unravel mechanistically how MYCN plays a critical role in the early transformation of the tNCCs using transcriptomics and epigenomic based approaches. The survival outcome of high risk NB patients is still 50% which warrant for developing novel drugs for the treatment. We have developed unique NB model system in the Lab to understand MYCN mediated changes in gene expression during early tNCC development. We showed evidence that MYCN interacts with RNA-modification machinery, and this has functional consequences in creating undifferentiated state in NB. Based on initial finding we would like to understand how RNA-modification crosstalk with epigenetic driven mechanisms contributing further to NB disease mechanisms. We have standardized methods to profile RNA modification using low-input RNA and this will be instrumental in implementing RNA-modification profiling in NB tumors. We aim profile RNA-modifications along with epigenetic marks in NB tumors and this will allow us to connect our mechanistic data to the clinical features of NB. The current proposal along with the strong foundation of preliminary data has the potential to take forward the observation of the basic biology to the development of novel therapeutic intervention for NBs.