MYCN and the epigenome
Open Access
- 1 January 2013
- journal article
- review article
- Published by Frontiers Media SA in Frontiers in Oncology
- Vol. 3, 42541
- https://doi.org/10.3389/fonc.2013.00001
Abstract
It is well known that Neuroblastoma (NB) patients whose tumors have an undifferentiated histology and a transcriptome enriched in cell cycle genes have a worse prognosis. This contrasts with the good prognoses of patients whose tumors have histologic evidence of differentiation and a transcriptome enriched in differentiation genes. Tumor cell lines from poor prognosis, high-risk patients contain a number of genetic alterations, including amplification of MYCN, 1pLOH, and unbalanced 11q or gains of Chr 17 and 7, and exhibit uncontrolled growth and an undifferentiated phenotype in in vitro culture. Yet treatment of such NB cell lines with retinoic acid results in growth control and induction of differentiation. This indicates that the signaling pathways that regulate cell growth and differentiation are not functionally lost but dysregulated. Agents such as retinoic acid normalize the signaling pathways and impose growth control and induction of differentiation. Recent studies in embryonic stem cells indicate that polycomb repressor complex proteins (PRC1 and PRC2) play a major role in regulating stem cell lineage specification and coordinating the shift from a transcriptome that supports self-renewal or growth to one that specifies lineage and controls growth. We have shown that in NB, the PRC2 complex is elevated in undifferentiated NB tumors and functions to suppress a number of tumor suppressor genes. This study will review the role of MYC genes in regulating the epigenome in normal development and explore how this role may be altered during tumorigenesis.This publication has 59 references indexed in Scilit:
- Nucleosomal Elements that Control the Topography of the Barrier to TranscriptionCell, 2012
- Transcriptional Amplification in Tumor Cells with Elevated c-MycCell, 2012
- Direct effects of Bmi1 on p53 protein stability inactivates oncoprotein stress responses in embryonal cancer precursor cells at tumor initiationOncogene, 2012
- N-Myc and GCN5 Regulate Significantly Overlapping Transcriptional Programs in Neural Stem CellsPLOS ONE, 2012
- EZH2 Mediates Epigenetic Silencing of Neuroblastoma Suppressor Genes CASZ1, CLU, RUNX3, and NGFRCancer Research, 2012
- A SP1/MIZ1/MYCN Repression Complex Recruits HDAC1 at the TRKA and p75NTR Promoters and Affects Neuroblastoma Malignancy by Inhibiting the Cell Response to NGFCancer Research, 2011
- Myc Regulation of mRNA Cap MethylationGenes & Cancer, 2010
- The c-MYC Oncoprotein Is a Substrate of the Acetyltransferases hGCN5/PCAF and TIP60Molecular and Cellular Biology, 2004
- An ATPase/Helicase Complex Is an Essential Cofactor for Oncogenic Transformation by c-MycMolecular Cell, 2000
- The Transcriptional Coactivators p300 and CBP Are Histone AcetyltransferasesCell, 1996