From DNA copy number gains and tumor dependencies to novel therapeutic targets for high-risk neuroblastoma Review
| Authors: | Decaesteker, B.; Durinck, K.; Van Roy, N.; De Wilde, B.; Van Neste, C.; Van Haver, S.; Roberts, S.; De Preter, K.; Vermeirssen, V.; Speleman, F. |
| Review Title: | From DNA copy number gains and tumor dependencies to novel therapeutic targets for high-risk neuroblastoma |
| 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. © 2021 by the authors. Licensee MDPI, Basel, Switzerland. |
| Keywords: | protein expression; unclassified drug; overall survival; gene deletion; review; nonhuman; cell proliferation; gene targeting; gene overexpression; microrna; gene expression profiling; protein protein interaction; genetic transcription; childhood cancer; carcinogenesis; tumor suppressor gene; neuroblastoma; chromosome translocation; gene control; cyclin d1; oncogene c myc; cell cycle regulation; bioinformatics; comparative genomic hybridization; chromosome 11; chromosome 17; transcription factor fkhrl1; zebra fish; cyclin dependent kinase 4; cyclin dependent kinase activating kinase; canonical wnt signaling; anaplastic lymphoma kinase; copy number variation; epistasis; transcription factor sox9; mycn; drug targets; pi3k/akt signaling; mapk signaling; microrna 17; human; whole genome sequencing; retinal pigment epithelium; coimmunoprecipitation; transcription factor tbx5; dependency; dna copy number gains; baculoviral iap repeat containing protein 5; transcription factor sox11; tripartite motif protein; tripartite motif protein 37 |
| Journal Title: | Journal of Personalized Medicine |
| Volume: | 11 |
| Issue: | 12 |
| ISSN: | 2075-4426 |
| Publisher: | MDPI |
| Date Published: | 2021-12-01 |
| Start Page: | 1286 |
| Language: | English |
| DOI: | 10.3390/jpm11121286 |
| PROVIDER: | scopus |
| PMCID: | PMC8707517 |
| PUBMED: | 34945759 |
| DOI/URL: | |
| Notes: | Review -- Export Date: 1 February 2022 -- Source: Scopus |
