The MYCN Protein in Health and Disease

Abstract

MYCN is a member of the MYC family of proto-oncogenes. It encodes a transcription factor, MYCN, involved in the control of fundamental processes during embryonal development. The MYCN protein is situated downstream of several signaling pathways promoting cell growth, proliferation and metabolism of progenitor cells in different developing organs and tissues. Conversely, deregulated MYCN signaling supports the development of several different tumors, mainly with a childhood onset, including neuroblastoma, medulloblastoma, rhabdomyosarcoma and Wilms’ tumor, but it is also associated with some cancers occurring during adulthood such as prostate and lung cancer. In neuroblastoma, MYCN-amplification is the most consistent genetic aberration associated with poor prognosis and treatment failure. Targeting MYCN has been proposed as a therapeutic strategy for the treatment of these tumors and great efforts have allowed the development of direct and indirect MYCN inhibitors with potential clinical use.

Exosomal miRNA Cargo as Mediator of Immune Escape Mechanisms in Neuroblastoma

“…Although the etiology of neuroblastoma is not completely understood, a number of genetic alterations are present in both familial and sporadic neuroblastoma. Among the genes most frequently altered in neuroblastoma is MYCN, which is amplified in about 25% of all neuroblastoma cases and whose expression positively correlates with advanced disease stage (1). High levels of MYCN protein in neuroblastoma patients correlate with metastasis and other hallmarks of poor prognosis (2).…”

Bioinformatic analysis reveals MIR502 as a potential tumour suppressor in ovarian cancer

“…In neuroblastoma, a genetic aberration of MYCN ampli cation is related to a poor prognosis and failure of therapy. MYCN targeted therapy has been proposed as a new strategy for cancer treatment, and many effort has been made to develop direct and indirect MYCN inhibitors with potential clinical applications [45].…”

Retinoblastoma, the visible CNS tumor: A review

“…Despite this, a small fraction of unilateral cases lack identified RB1 mutations, so it was long postulated that an alternative mechanism of retinoblastoma genesis might be possible. As part of an international team, in 2013 we identified that 1.4% of unilateral retinoblastoma, lacking RB1 mutations, instead showed amplification of MYCN (Rushlow et al, ) (Figure ), a transcription factor–encoding gene more frequently associated with the pediatric peripheral nervous system tumor, neuroblastoma (Ruiz‐Perez, Henley, & Arsenian‐Henriksson, ). This finding raises interesting questions about the parallels between retinoblastoma and other neuronal tumors (see below).…”