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Epigenetic Post transcriptional Mutation in Neuro-Oncology

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Epigenetic Advancements in Cancer

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Abstract

Epigenetics referred to the hereditary changes in gene expression at the level of mitosis, which are different from the changes in DNA sequences whereas epigenetic variation involves CpG Island (CGI) hypermethylation along with the silencing of tumor suppressor genes in case of brain tumors. In DNA methylation, cytosine nucleotides are methylated at fifth position of the pyrimidine ring when they are part of the symmetrical dinucleotide CpG. Each post-embryonic cell has a specific level of DNA methylation whereas an overall decrease in the methylation level in the genome is termed as hypomethylation. As repeated sequences (such as CpG) are ideal recombination sites, hypomethylation promotes mitotic recombination, but it increases with aging process. However, some CpG sites such as CpG islands (CGI) are not methylated in normal cells whereas in cancer cells, methylation of CGI is frequently observed in the promoter region of various genes dispersed throughout the genome. This state of methylation is known as hypermethylation and it induces silencing of the corresponding gene (usually tumor suppressor genes) either by directly inhibiting the binding of transcription factors or changing the chromatin structure by recruiting histone deacetylases. DNA hypomethylation and hypermethylation usually coexist in the same genome but at different sequences in a tumor cell.

Further, induced gene expression and protein function attributes to abrogated cell cycle leading to uncontrolled cell division and tumor growth, which invade into the nearby normal brain parenchyma cells. There are two major processes that regulate epigenesis, for instance, covalent modification of DNA and amino-acids present on histone. Apart from post-transcriptional histone modification and DNA methylation, other epigenetic variations include non-coding RNAs, chromatin modeling and remodeling. Epigenetic variations in the normal brain cells are the major cause of gliomas whereas particular variations in tumor aggression determine its response to therapy and survival rate of the patients. Similarly, epigenetic variations have been implicated in the pathogenesis of several neurodegenerative disorders (NDD) including Alzheimer’s disease (AD), Parkinson’s disease (PD), Poly Q diseases and have been shown to determine onset, latency and period of disease progression in NDD. From the various studies, an important epigenetic intervention came under the consideration, for instance, drugs that are normally used for clinical trials target Histone Deacetylase (HDAC) and termed as Histone Deacetylase Inhibitors (HDACi). In this chapter, we described the mechanism of epigenetic processes in the normal cells, their aberrations that linked to gliomas and other neurodegenerative disorders. Further, we discussed the potential role of epigenetic therapies in the amelioration of neuro-oncology and neurodegenerative disorders.

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Authors and Affiliations

  1. Molecular Neuroscience and Functional Genomics Laboratory, Delhi Technological University (Formerly Delhi College of Engineering), New Delhi, Delhi, 110042, India

    Ankit Tripathi, Renu Sharma, Noopur Kejriwal, Rashmi K. Ambasta & Pravir Kumar

  2. Department of Neurology, Tufts University School of Medicine, Boston, MA, USA

    Pravir Kumar

  3. Department of Biotechnology, Mechanical Engineering Building, Delhi Technological University (Formerly Delhi College of Engineering), Room # FW4TF3, Shahbad Daulatpur, Bawana Road, New Delhi, Delhi, 110042, India

    Pravir Kumar

Authors
  1. Ankit Tripathi
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  2. Renu Sharma
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  3. Noopur Kejriwal
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  4. Rashmi K. Ambasta
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  5. Pravir Kumar
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Correspondence to Pravir Kumar .

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Editors and Affiliations

  1. Department of Biological Sciences, Alabama State University, Montgomery, Alabama, USA

    Manoj K. Mishra

  2. School of Medicine, Washington University, St. Louis, Missouri, USA

    Kumar S. Bishnupuri

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Tripathi, A., Sharma, R., Kejriwal, N., Ambasta, R.K., Kumar, P. (2016). Epigenetic Post transcriptional Mutation in Neuro-Oncology. In: Mishra, M., Bishnupuri, K. (eds) Epigenetic Advancements in Cancer. Springer, Cham. https://doi.org/10.1007/978-3-319-24951-3_8

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