4610

MYCL1

LMYC|MYCL|bHLHe38;v-myc myelocytomatosis viral oncogene homolog 1, lung carcinoma derived (avian);MYCL1;v-myc myelocytomatosis viral oncogene homolog 1, lung carcinoma derived (avian)

class E basic helix-loop-helix protein 38|l-myc-1 proto-oncogene|myc-related gene from lung cancer|protein L-Myc-1

1p34.2

protein-coding

Multiple genetic changes take place during tumor development and progression. These genetic changes result in inactivation of tumor suppressor genes and activation of proto-oncogenes. Frequent genetic changes observed in gliomas are losses of chromosomal regions on 9p, 10q, 13q, 17p and on 22. Loss of 10q is seen in more than 80% of the glioblastoma multiforme (GBM) tumors suggesting the presence of a gene critical for GBM formation on this chromosome. Amplification of epidermal growth factor receptor gene and expression of platelet derived growth factor and fibroblast growth factor genes are also common among gliomas. The most common genetic abnormality found in medulloblastomas is loss of 17p. The C-myc gene is amplified in a few primary tumors, but the incidence of amplification is higher in medulloblastoma derived cell lines. These findings suggest that the same two genetic processes, gene amplification and regional chromosomal loss, which characterize other primitive childhood neuroectodermal tumors such as retinoblastoma and neuroblastoma are also important in medulloblastomas.

Myc proteins (c-myc, Mycn and Mycl) target proliferative and apoptotic pathways vital for progression in cancer. Amplification of the MYCN gene has emerged as one of the clearest indicators of aggressive and chemotherapy-refractory diseasein children with neuroblastoma, the most common extracranial solid tumor of childhood. Phosphorylation and ubiquitin-mediated modulation of Myc protein influence stability and represent potential targets for therapeutic intervention. Phosphorylation of Myc proteins is controlled in-part by the receptor tyrosine kinase/phosphatidylinositol 3-kinase/Akt/mTOR signaling, with additional contributions from Aurora A kinase. Myc proteins regulate apoptosis in part through interactions with the p53/Mdm2/Arf signaling pathway. mutation in p53 iscommonly observed in patients with relapsed neuroblastoma, contributing to both biology and therapeutic resistance. This review examines Myc function and regulation in neuroblastoma, and discusses emerging therapies that target Mycn.