Neuroblastoma and the epigenome

Neuroblastoma (NB) is a pediatric cancer of the sympathetic nervous system and one of the most common solid tumors in infancy. Amplification of MYCN , copy number alterations, numerical and segmental chromosomal aberrations, mutations, and rearrangements on a handful of genes, such as ALK , ATRX , T...

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Bibliographic Details
Published in:Cancer and metastasis reviews 2021-03, Vol.40 (1), p.173-189
Main Authors: Fetahu, Irfete S., Taschner-Mandl, Sabine
Format: Article
Language:English
Subjects:
Biomedical and Life Sciences
Biomedicine
Cancer Research
Child
Chromatin
Chromosome aberrations
Copy number
Demethylation
Deoxyribonucleic acid
Development and progression
DNA
DNA Methylation
Embryogenesis
Epigenesis, Genetic
Epigenetic inheritance
Epigenetics
Epigenome
Gene expression
Genes
Genetic factors
Genomic imprinting
Histone Deacetylases - metabolism
Histones
Humans
MAP kinase
Methylation
Methyltransferases
Mutation
Neuroblastoma
Neuroblastoma - genetics
Non-coding RNA
Non-Thematic Review
Oncology
p53 Protein
Solid tumors
Sympathetic nervous system
Tumor proteins
Tumorigenesis
Vorinostat
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Summary:Neuroblastoma (NB) is a pediatric cancer of the sympathetic nervous system and one of the most common solid tumors in infancy. Amplification of MYCN , copy number alterations, numerical and segmental chromosomal aberrations, mutations, and rearrangements on a handful of genes, such as ALK , ATRX , TP53 , RAS/MAPK pathway genes, and TERT , are attributed as underlying causes that give rise to NB. However, the heterogeneous nature of the disease—along with the relative paucity of recurrent somatic mutations—reinforces the need to understand the interplay of genetic factors and epigenetic alterations in the context of NB. Epigenetic mechanisms tightly control gene expression, embryogenesis, imprinting, chromosomal stability, and tumorigenesis, thereby playing a pivotal role in physio- and pathological settings. The main epigenetic alterations include aberrant DNA methylation, disrupted patterns of posttranslational histone modifications, alterations in chromatin composition and/or architecture, and aberrant expression of non-coding RNAs. DNA methylation and demethylation are mediated by DNA methyltransferases (DNMTs) and ten-eleven translocation (TET) proteins, respectively, while histone modifications are coordinated by histone acetyltransferases and deacetylases (HATs, HDACs), and histone methyltransferases and demethylases (HMTs, HDMs). This article focuses predominately on the crosstalk between the epigenome and NB, and the implications it has on disease diagnosis and treatment.
ISSN:0167-7659
1573-7233
DOI:10.1007/s10555-020-09946-y