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From DNA Copy Number Gains and Tumor Dependencies to Novel Therapeutic Targets for High-Risk Neuroblastoma

Neuroblastoma is a pediatric tumor arising from the sympatho-adrenal lineage and a worldwide leading cause of childhood cancer-related deaths. About half of high-risk patients die from the disease while survivors suffer from multiple therapy-related side-effects. While neuroblastomas present with a...

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Autores principales: Decaesteker, Bieke, Durinck, Kaat, Van Roy, Nadine, De Wilde, Bram, Van Neste, Christophe, Van Haver, Stéphane, Roberts, Stephen, De Preter, Katleen, Vermeirssen, Vanessa, Speleman, Frank
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8707517/
https://www.ncbi.nlm.nih.gov/pubmed/34945759
http://dx.doi.org/10.3390/jpm11121286
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author Decaesteker, Bieke
Durinck, Kaat
Van Roy, Nadine
De Wilde, Bram
Van Neste, Christophe
Van Haver, Stéphane
Roberts, Stephen
De Preter, Katleen
Vermeirssen, Vanessa
Speleman, Frank
author_facet Decaesteker, Bieke
Durinck, Kaat
Van Roy, Nadine
De Wilde, Bram
Van Neste, Christophe
Van Haver, Stéphane
Roberts, Stephen
De Preter, Katleen
Vermeirssen, Vanessa
Speleman, Frank
author_sort Decaesteker, Bieke
collection PubMed
description Neuroblastoma is a pediatric tumor arising from the sympatho-adrenal lineage and a worldwide leading cause of childhood cancer-related deaths. About half of high-risk patients die from the disease while survivors suffer from multiple therapy-related side-effects. While neuroblastomas present with a low mutational burden, focal and large segmental DNA copy number aberrations are highly recurrent and associated with poor survival. It can be assumed that the affected chromosomal regions contain critical genes implicated in neuroblastoma biology and behavior. More specifically, evidence has emerged that several of these genes are implicated in tumor dependencies thus potentially providing novel therapeutic entry points. In this review, we briefly review the current status of recurrent DNA copy number aberrations in neuroblastoma and provide an overview of the genes affected by these genomic variants for which a direct role in neuroblastoma has been established. Several of these genes are implicated in networks that positively regulate MYCN expression or stability as well as cell cycle control and apoptosis. Finally, we summarize alternative approaches to identify and prioritize candidate copy-number driven dependency genes for neuroblastoma offering novel therapeutic opportunities.
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spelling pubmed-87075172021-12-25 From DNA Copy Number Gains and Tumor Dependencies to Novel Therapeutic Targets for High-Risk Neuroblastoma Decaesteker, Bieke Durinck, Kaat Van Roy, Nadine De Wilde, Bram Van Neste, Christophe Van Haver, Stéphane Roberts, Stephen De Preter, Katleen Vermeirssen, Vanessa Speleman, Frank J Pers Med Review Neuroblastoma is a pediatric tumor arising from the sympatho-adrenal lineage and a worldwide leading cause of childhood cancer-related deaths. About half of high-risk patients die from the disease while survivors suffer from multiple therapy-related side-effects. While neuroblastomas present with a low mutational burden, focal and large segmental DNA copy number aberrations are highly recurrent and associated with poor survival. It can be assumed that the affected chromosomal regions contain critical genes implicated in neuroblastoma biology and behavior. More specifically, evidence has emerged that several of these genes are implicated in tumor dependencies thus potentially providing novel therapeutic entry points. In this review, we briefly review the current status of recurrent DNA copy number aberrations in neuroblastoma and provide an overview of the genes affected by these genomic variants for which a direct role in neuroblastoma has been established. Several of these genes are implicated in networks that positively regulate MYCN expression or stability as well as cell cycle control and apoptosis. Finally, we summarize alternative approaches to identify and prioritize candidate copy-number driven dependency genes for neuroblastoma offering novel therapeutic opportunities. MDPI 2021-12-03 /pmc/articles/PMC8707517/ /pubmed/34945759 http://dx.doi.org/10.3390/jpm11121286 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Decaesteker, Bieke
Durinck, Kaat
Van Roy, Nadine
De Wilde, Bram
Van Neste, Christophe
Van Haver, Stéphane
Roberts, Stephen
De Preter, Katleen
Vermeirssen, Vanessa
Speleman, Frank
From DNA Copy Number Gains and Tumor Dependencies to Novel Therapeutic Targets for High-Risk Neuroblastoma
title From DNA Copy Number Gains and Tumor Dependencies to Novel Therapeutic Targets for High-Risk Neuroblastoma
title_full From DNA Copy Number Gains and Tumor Dependencies to Novel Therapeutic Targets for High-Risk Neuroblastoma
title_fullStr From DNA Copy Number Gains and Tumor Dependencies to Novel Therapeutic Targets for High-Risk Neuroblastoma
title_full_unstemmed From DNA Copy Number Gains and Tumor Dependencies to Novel Therapeutic Targets for High-Risk Neuroblastoma
title_short From DNA Copy Number Gains and Tumor Dependencies to Novel Therapeutic Targets for High-Risk Neuroblastoma
title_sort from dna copy number gains and tumor dependencies to novel therapeutic targets for high-risk neuroblastoma
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8707517/
https://www.ncbi.nlm.nih.gov/pubmed/34945759
http://dx.doi.org/10.3390/jpm11121286
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