MYC-family protein overexpression and prominent nucleolar formation represent prognostic indicators and potential therapeutic targets for aggressive high-MKI neuroblastomas: a report from the children's oncology group

Oncotarget
Risa Niemas-TeshibaHiroyuki Shimada

Abstract

Neuroblastomas with a high mitosis-karyorrhexis index (High-MKI) are often associated with MYCN amplification, MYCN protein overexpression and adverse clinical outcome. However, the prognostic effect of MYC-family protein expression on these neuroblastomas is less understood, especially when MYCN is not amplified. To address this, MYCN and MYC protein expression in High-MKI cases (120 MYCN amplified and 121 non-MYCN amplified) was examined by immunohistochemistry. The majority (101) of MYCN-amplified High-MKI tumors were MYCN(+), leaving one MYC(+), 2 both(+), and 16 both(-)/(+/-), whereas non-MYCN-amplified cases appeared heterogeneous, including 7 MYCN(+), 36 MYC(+), 3 both(+), and 75 both(-)/(+/-) tumors. These MYC-family proteins(+), or MYC-family driven tumors, were most likely to have prominent nucleolar (PN) formation (indicative of augmented rRNA synthesis). High-MKI neuroblastoma patients showed a poor survival irrespective of MYCN amplification. However, patients with MYC-family driven High-MKI neuroblastomas had significantly lower survival than those with non-MYC-family driven tumors. MYCN(+), MYC-family protein(+), PN(+), and clinical stage independently predicted poor survival. Specific inhibition of hyperactive r...Continue Reading

References

Apr 1, 1991·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·A T LookG M Brodeur
Aug 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·N IkegakiR H Kennett
Apr 1, 1989·Japanese Journal of Cancer Research : Gann·T JinboS Sawaguchi
Oct 31, 1985·The New England Journal of Medicine·R C SeegerD Hammond
Oct 4, 1995·Journal of the National Cancer Institute·H ShimadaR C Seeger
Aug 1, 1993·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·G M BrodeurF Hedborg
Nov 5, 1997·Journal of Pediatric Hematology/oncology·J G GurneyL L Robison
Sep 27, 2000·Proceedings of the National Academy of Sciences of the United States of America·S KimL A Lee
May 30, 2003·The Oncologist·Joanna L WeinsteinSusan L Cohn
Aug 24, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·W B LondonS L Cohn
Nov 25, 2005·The New England Journal of Medicine·Edward F AttiyehUNKNOWN Children's Oncology Group
May 26, 2006·The EMBO Journal·Paul S KnoepflerRobert N Eisenman
Jun 30, 2007·The EMBO Journal·Mu-Shui DaiHua Lu
Dec 3, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Susan L CohnUNKNOWN INRG Task Force
Mar 25, 2010·Nature Reviews. Cancer·Jan van RiggelenDean W Felsher
Sep 3, 2010·International Journal of Oncology·Jaime TorresXao X Tang
Oct 1, 2011·Nature Protocols·Danielle N RockwoodDavid L Kaplan
Feb 14, 2012·Nature Chemical Biology·Tracy L KellerMalcolm Whitman
Apr 3, 2012·Cell·Chi V Dang
Oct 9, 2012·Nature Genetics·Jan J MolenaarJohannes H Schulte
Apr 25, 2013·Nature Reviews. Cancer·Megan J BywaterRoss D Hannan
Aug 3, 2013·Cold Spring Harbor Perspectives in Medicine·Chi V Dang
Aug 21, 2013·Trends in Molecular Medicine·Nadine HeinRoss D Hannan
Mar 13, 2014·Oncogene·G PoortingaR D Hannan
May 27, 2014·Biochimica Et Biophysica Acta·Daniel DiolaitiRobert N Eisenman
Sep 11, 2014·Pediatric and Developmental Pathology : the Official Journal of the Society for Pediatric Pathology and the Paediatric Pathology Society·Risa TeshibaHiroyuki Shimada
Sep 19, 2015·Cancer Discovery·Zachary E StineChi V Dang
Oct 27, 2015·Journal of Controlled Release : Official Journal of the Controlled Release Society·Jeannine M CoburnDavid L Kaplan

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Citations

Nov 28, 2018·Current Opinion in Pediatrics·Suzanne MacFarland, Rochelle Bagatell
Apr 21, 2020·Pediatric Blood & Cancer·Jason R HealyRobert W Schnepp
Dec 17, 2019·JCO Precision Oncology·Naohiko IkegakiUNKNOWN International Neuroblastoma Pathology Committee
Aug 15, 2018·Histochemistry and Cell Biology·Dariusz Stępiński
Feb 23, 2019·Journal of the National Cancer Institute·Derek A OldridgeKatherine K Matthay
Mar 19, 2019·Journal of Pediatric Surgery·Jordan S TaylorBill Chiu

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Methods Mentioned

BETA
histone acetylation
xenografts

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