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From DNA copy number gains and tumor dependencies to novel therapeutic targets for high-risk neuroblastoma

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Abstract
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.
Keywords
Medicine (miscellaneous), neuroblastoma, DNA copy number gains, MYCN, dependency, drug targets, P53/MDM2/P14(ARF) PATHWAY, MULTIDRUG-RESISTANCE, ACTIVATING MUTATIONS, MICRORNA CLUSTER, HIGH EXPRESSION, HIGH-FREQUENCY, ALK KINASE, 17Q GAIN, MYCN, GENE

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MLA
Decaesteker, Bieke, et al. “From DNA Copy Number Gains and Tumor Dependencies to Novel Therapeutic Targets for High-Risk Neuroblastoma.” JOURNAL OF PERSONALIZED MEDICINE, vol. 11, no. 12, 2021, doi:10.3390/jpm11121286.
APA
Decaesteker, B., Durinck, K., Van Roy, N., De Wilde, B., Van Neste, C., Van Haver, S., … Speleman, F. (2021). From DNA copy number gains and tumor dependencies to novel therapeutic targets for high-risk neuroblastoma. JOURNAL OF PERSONALIZED MEDICINE, 11(12). https://doi.org/10.3390/jpm11121286
Chicago author-date
Decaesteker, Bieke, Kaat Durinck, Nadine Van Roy, Bram De Wilde, Christophe Van Neste, Stéphane Van Haver, Stephen Roberts, Katleen De Preter, Vanessa Vermeirssen, and Franki Speleman. 2021. “From DNA Copy Number Gains and Tumor Dependencies to Novel Therapeutic Targets for High-Risk Neuroblastoma.” JOURNAL OF PERSONALIZED MEDICINE 11 (12). https://doi.org/10.3390/jpm11121286.
Chicago author-date (all authors)
Decaesteker, Bieke, Kaat Durinck, Nadine Van Roy, Bram De Wilde, Christophe Van Neste, Stéphane Van Haver, Stephen Roberts, Katleen De Preter, Vanessa Vermeirssen, and Franki Speleman. 2021. “From DNA Copy Number Gains and Tumor Dependencies to Novel Therapeutic Targets for High-Risk Neuroblastoma.” JOURNAL OF PERSONALIZED MEDICINE 11 (12). doi:10.3390/jpm11121286.
Vancouver
1.
Decaesteker B, Durinck K, Van Roy N, De Wilde B, Van Neste C, Van Haver S, et al. From DNA copy number gains and tumor dependencies to novel therapeutic targets for high-risk neuroblastoma. JOURNAL OF PERSONALIZED MEDICINE. 2021;11(12).
IEEE
[1]
B. Decaesteker et al., “From DNA copy number gains and tumor dependencies to novel therapeutic targets for high-risk neuroblastoma,” JOURNAL OF PERSONALIZED MEDICINE, vol. 11, no. 12, 2021.
@article{8729961,
  abstract     = {{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.}},
  articleno    = {{1286}},
  author       = {{Decaesteker, Bieke and Durinck, Kaat and Van Roy, Nadine and De Wilde, Bram and Van Neste, Christophe and Van Haver, Stéphane and Roberts, Stephen and De Preter, Katleen and Vermeirssen, Vanessa and Speleman, Franki}},
  issn         = {{2075-4426}},
  journal      = {{JOURNAL OF PERSONALIZED MEDICINE}},
  keywords     = {{Medicine (miscellaneous),neuroblastoma,DNA copy number gains,MYCN,dependency,drug targets,P53/MDM2/P14(ARF) PATHWAY,MULTIDRUG-RESISTANCE,ACTIVATING MUTATIONS,MICRORNA CLUSTER,HIGH EXPRESSION,HIGH-FREQUENCY,ALK KINASE,17Q GAIN,MYCN,GENE}},
  language     = {{eng}},
  number       = {{12}},
  pages        = {{25}},
  title        = {{From DNA copy number gains and tumor dependencies to novel therapeutic targets for high-risk neuroblastoma}},
  url          = {{http://doi.org/10.3390/jpm11121286}},
  volume       = {{11}},
  year         = {{2021}},
}

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