Neuroblastoma-derived v-myc avian myelocytomatosis viral related oncogene orMYCNgene

Abstract

TheMYCNgene belongs to the MYC family of transcription factors. Amplification ofMYCN, first discovered in neuroblastoma cells, ushered in the era of cancer genomics. TheMYCNgene and MYCN protein are extensively studied in the context of neuroblastoma. As demonstrated in transgenic mouse models,MYCNgene shows a restricted spatiotemporal expression predominantly in the neural crest cells which explains the associated neoplasms including neuroblastoma and central nervous system tumours. In neuroblastoma,MYCNamplification is a marker of aggressive tumours with poor prognosis and survival and forms the basis of risk stratification classifications.MYCNdysregulated expression occurs by several mechanisms at the transcriptional, translational and post-translational levels. These include massive gene amplification which occurs in an extrachromosomal location, upregulated transcription and stabilisation of the protein increasing its half-life. MYCN protein, a basic loop-helix-loop leucine zipper transcription factor, has many regions which bind to several proteins foremost of which is MAX forming the MYC:MAX heterodimer. Overall, MYCN controls multiple aspects of cell fate, foremost of which is cellular proliferation besides cell differentiation, apoptosis and cellular metabolism, all of which are the focus of this brief review. In addition to amplification, other mechanisms of MYCN overexpression include activating missense mutations as reported in basal cell carcinoma and Wilms tumour. A better understanding of this molecule will help in the discovery of novel strategies for its indirect targeting to improve the outcomes of patients with neuroblastoma and other MYCN-associated neoplasms.