Journal
CANCER AND METASTASIS REVIEWS
Volume 40, Issue 1, Pages 173-189Publisher
SPRINGER
DOI: 10.1007/s10555-020-09946-y
Keywords
Epigenetics; DNA methylation; Histone modifications; MicroRNAs; Chromatin remodeling; Neuroblastoma
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Funding
- FWF Austrian Science Fund [I 4162]
- Vienna Science and Technology Fund [WTF LS18-111]
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Neuroblastoma is a common solid tumor in infants, with genetic and epigenetic alterations playing a key role in its pathogenesis. Aberrant DNA methylation, disrupted histone modification patterns, and abnormal expression of non-coding RNAs are major epigenetic changes associated with NB.
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.
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