Neuroblastoma and MYCN.
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Journal: 2014/May - Cold Spring Harbor perspectives in medicine
ISSN: 2157-1422
Abstract:
Neuroblastoma, the most common extracranial solid tumor of childhood, is thought to originate from undifferentiated neural crest cells. Amplification of the MYC family member, MYCN, is found in ∼25% of cases and correlates with high-risk disease and poor prognosis. Currently, amplification of MYCN remains the best-characterized genetic marker of risk in neuroblastoma. This article reviews roles for MYCN in neuroblastoma and highlights recent identification of other driver mutations. Strategies to target MYCN at the level of protein stability and transcription are also reviewed.
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Cold Spring Harb Perspect Med 3(10): a014415
PMID: 24086065

Neuroblastoma and MYCN

Departments of Neurology, Pediatrics, and Neurosurgery, University of California, San Francisco, California 94158-9001
Correspondence:moc.liamg@ssiewaw
Departments of Neurology, Pediatrics, and Neurosurgery, University of California, San Francisco, California 94158-9001
Correspondence:moc.liamg@ssiewaw
Copyright © 2013 Cold Spring Harbor Laboratory Press; all rights reserved

Abstract

Neuroblastoma, the most common extracranial solid tumor of childhood, is thought to originate from undifferentiated neural crest cells. Amplification of the MYC family member, MYCN, is found in ∼25% of cases and correlates with high-risk disease and poor prognosis. Currently, amplification of MYCN remains the best-characterized genetic marker of risk in neuroblastoma. This article reviews roles for MYCN in neuroblastoma and highlights recent identification of other driver mutations. Strategies to target MYCN at the level of protein stability and transcription are also reviewed.

Abstract

Neuroblastoma, described by James Wright in 1910, was named because cells were associated with fibrils in arrangements similar to neuroblasts. Nine of 12 cases were in children, suggesting the disease manifests early in life from primitive undifferentiated cells (Wright 1910). Today, neuroblastoma ranks as the most common cancer in infants (<1 year old), with 90% of cases diagnosed by age 5. The primary tumor is frequently located in tissues originating from the sympathetic nervous system, adrenal medulla, or paraspinal ganglia, and metastases are found in a majority of cases at diagnosis, consistent with an origin from multipotent migratory neural crest cells.

Tumor susceptibility SNPs were identified in BARD1 (Capasso et al. 2009; Nguyen et al. 2011; Diskin et al. 2012), HACE1 (Diskin et al. 2012), LMO1 (Wang et al. 2011; Diskin et al. 2012; Nguyen et al. 2011), and LIN28B (Diskin et al. 2012). Pugh et al. (2013) identified other genetic mutations that had frequencies <1%.

References: Molenaar et al. 2012b, Chen et al. 2008, George et al. 2008, Pugh et al. 2013, Mossé et al. 2008, Sausen et al. 2013. Cheung et al. 2012, Molenaar et al. 2012a, Bentires-Alj et al. 2004.

Half of tumors with ATRX mutations were from older patients, which account for a small percentage of neuroblastoma patients.

ACKNOWLEDGMENTS

We thank Yvan Chanthery, Justin Chen, William Clay Gustafson, Paul Knoepfler, and Jasmine Lau for critical review. M.H. is supported by the Pediatric Brain Tumor Foundation, and by a Postdoctoral Fellowship, PF-13-295-01—TBG from the American Cancer Society. The Weiss Laboratory is supported by National Institutes of Health grants CA133091, CA102321, CA128583, CA148699, CA159859, CA163155, CA081403, the Cancer League, and the Alex's Lemonade Stand, Katie Dougherty, Pediatric Brain Tumor, St Baldrick's, and Samuel G. Waxman Foundations. This review provides only a sampling of literature available on this topic. We apologize to investigators whose works we failed to cite.

ACKNOWLEDGMENTS

Footnotes

Editors: Chi V. Dang and Robert N. Eisenman

Additional Perspectives on MYC and the Pathway to Cancer available at www.perspectivesinmedicine.org

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