Neuroblastoma and MYCN
Miller Huang,William A. Weiss +1 more
TLDR
Roles for MYCN in neuroblastoma are reviewed and recent identification of other driver mutations are highlighted, as well as strategies to target MYCN at the level of protein stability and transcription.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.read more
Citations
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Neuroblastoma
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References
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Journal ArticleDOI
Induction of apoptosis in fibroblasts by c-myc protein
Gerard I. Evan,Andrew H. Wyllie,Christopher S. Gilbert,Trevor Littlewood,Hartmut Land,Mary W. Brooks,Catherine M. Waters,Linda Z. Penn,David C. Hancock +8 more
TL;DR: It is demonstrated that deregulated c-myc expression induces apoptosis in cells growth arrested by a variety of means and at various points in the cell cycle.
Journal ArticleDOI
BET Bromodomain Inhibition as a Therapeutic Strategy to Target c-Myc
Jake Delmore,Ghayas C Issa,Madeleine E. Lemieux,Peter B. Rahl,Junwei Shi,Hannah M. Jacobs,Efstathios Kastritis,Timothy Gilpatrick,Ronald M. Paranal,Jun Qi,Marta Chesi,Anna C. Schinzel,Michael R. McKeown,Timothy P. Heffernan,Christopher R. Vakoc,P. Leif Bergsagel,Irene M. Ghobrial,Paul G. Richardson,Richard A. Young,William C. Hahn,William C. Hahn,Kenneth C. Anderson,Andrew L. Kung,James E. Bradner,Constantine S. Mitsiades +24 more
TL;DR: In this paper, a small-molecule bromodomain inhibitor, JQ1, was used to identify BET proteins as regulatory factors for c-Myc oncoprotein.
Journal ArticleDOI
Amplification of N-myc in untreated human neuroblastomas correlates with advanced disease stage
Garrett M. Brodeur,Robert C. Seeger,Robert C. Seeger,Manfred Schwab,Harold E. Varmus,J M Bishop +5 more
TL;DR: N-myc amplification is highly correlated with advanced stages of disease (P less than 0.001) and with the ability to grow in vitro as an established cell line, both of which are associated with a poor prognosis.
Journal ArticleDOI
Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma
Jeremy Schwartzentruber,Andrey Korshunov,Xiaoyang Liu,David T.W. Jones,Elke Pfaff,Karine Jacob,Dominik Sturm,Adam M. Fontebasso,Dong Anh Khuong Quang,Martje Tönjes,Volker Hovestadt,Steffen Albrecht,Marcel Kool,André Nantel,Carolin Konermann,Anders Lindroth,Natalie Jäger,Tobias Rausch,Marina Ryzhova,Jan O. Korbel,Thomas Hielscher,Peter Hauser,Miklós Garami,Almos Klekner,László Bognár,Martin Ebinger,Martin U. Schuhmann,Wolfram Scheurlen,Arnulf Pekrun,Michael C. Frühwald,Wolfgang Roggendorf,CM Kramm,Matthias Dürken,Jeffrey Atkinson,Pierre Lepage,Alexandre Montpetit,Magdalena Zakrzewska,Krzystof Zakrzewski,Pawel P. Liberski,Zhifeng Dong,Peter M. Siegel,Andreas E. Kulozik,Marc Zapatka,Abhijit Guha,David Malkin,Jörg Felsberg,Guido Reifenberger,Andreas von Deimling,Andreas von Deimling,Koichi Ichimura,V. Peter Collins,Hendrik Witt,Hendrik Witt,Till Milde,Till Milde,Olaf Witt,Olaf Witt,Cindy Zhang,Pedro Castelo-Branco,Peter Lichter,Damien Faury,Uri Tabori,Christoph Plass,Jacek Majewski,Stefan M. Pfister,Stefan M. Pfister,Nada Jabado +66 more
TL;DR: The presence of H3F3A/ATRX-DAXX/TP53 mutations was strongly associated with alternative lengthening of telomeres and specific gene expression profiles, suggesting that defects of the chromatin architecture underlie paediatric and young adult GBM pathogenesis.
Journal ArticleDOI
Association of multiple copies of the N-myc oncogene with rapid progression of neuroblastomas.
Robert C. Seeger,Garrett M. Brodeur,Harland N. Sather,Andree Dalton,Stuart E. Siegel,Kwan Y. Wong,Denman Hammond +6 more
TL;DR: The results suggest that genomic amplification of N-myc may have a key role in determining the aggressiveness of neuroblastomas.