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Epigenetic Regulation01:37

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Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
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Diploid organisms inherit genetic material through chromosomes from both parents. Copies of the same gene are known as alleles. In most cases, both alleles are simultaneously expressed and allow various cellular processes to function optimally. If one of the alleles is missing or mutated, the expression of the other allele can compensate; however, this is not true for all genes.
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Frequency and Prognostic Significance of Genetic Abnormalities in a Subgroup of Patients With Intermediate-Risk Neuroblastoma: A SIOPEN Study.

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Neuroblastoma and the epigenome.

Irfete S Fetahu1, Sabine Taschner-Mandl2

  • 1St. Anna Children's Cancer Research Institute, Zimmermannplatz 10, 1090, Vienna, Austria. irfete.fetahu@ccri.at.

Cancer Metastasis Reviews
|January 6, 2021
PubMed
Summary

Neuroblastoma (NB), a pediatric cancer, involves genetic factors and epigenetic alterations. Understanding epigenetics is crucial for NB diagnosis and treatment strategies.

Keywords:
Chromatin remodelingDNA methylationEpigeneticsHistone modificationsMicroRNAsNeuroblastoma

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Area of Science:

  • Pediatric Oncology
  • Cancer Epigenetics
  • Molecular Biology

Background:

  • Neuroblastoma (NB) is a common pediatric sympathetic nervous system cancer.
  • NB pathogenesis involves genetic alterations (e.g., MYCN amplification, gene mutations) and complex epigenetic dysregulation.
  • The heterogeneity of NB necessitates understanding the interplay between genetic and epigenetic factors.

Purpose of the Study:

  • To explore the critical role of epigenetic mechanisms in neuroblastoma development.
  • To highlight the implications of epigenetic alterations in NB diagnosis and therapeutic strategies.
  • To review the crosstalk between the neuroblastoma epigenome and its clinical impact.

Main Methods:

  • Review of current literature on neuroblastoma genetics and epigenetics.
  • Analysis of epigenetic alterations including DNA methylation, histone modifications, and non-coding RNAs.
  • Focus on the enzymes regulating epigenetic modifications (DNMTs, TETs, HATs, HDACs, HMTs, HDMs).

Main Results:

  • Epigenetic alterations such as aberrant DNA methylation and disrupted histone modifications are key in NB tumorigenesis.
  • Epigenetic mechanisms influence gene expression, embryogenesis, and chromosomal stability in NB.
  • Aberrant expression of non-coding RNAs also contributes to NB pathology.

Conclusions:

  • Epigenetic modifications are integral to neuroblastoma development and progression.
  • Targeting epigenetic pathways presents promising avenues for novel NB diagnostics and therapeutics.
  • Further research into the neuroblastoma epigenome is essential for improving patient outcomes.