This article is part of the Research Topic Targeting MYCN in paediatric cancers

Review ARTICLE

Front. Oncol., 25 January 2013 | doi: 10.3389/fonc.2013.00001

MYCN and the epigenome

  • Cell and Molecular Biology Section, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA

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.

Keywords: MYCN, EZH2, epigenetics, nucleosome, RNA polymerase II, HDAC, HAT, transcriptional activation

Citation: He S, Liu Z, Oh D-Y and Thiele CJ (2013) MYCN and the epigenome. Front. Oncol. 3:1. doi: 10.3389/fonc.2013.00001

Received: 13 December 2012; Accepted: 02 January 2013;
Published online: 25 January 2013.

Edited by:

Arturo Sala, Brunel University/University College London Institute of Child Health, UK

Reviewed by:

Arturo Sala, Brunel University/University College London Institute of Child Health, UK
Giovanni Perini, University of Bologna, Italy

Copyright: © 2013 He, Liu, Oh and Thiele. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.

*Correspondence: Carol J. Thiele, Cell and Molecular Biology Section, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, 10 Center Dr, CRC, 1W-3940, 20892 Bethesda, MD, USA. e-mail: ct47a@nih.gov

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