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Essay: The role of epigenetic modifiers in Non-Hodgkin B cell lymphoma

Kiewiet, M.B.G. (2013) Essay: The role of epigenetic modifiers in Non-Hodgkin B cell lymphoma. Master's Thesis / Essay, Biology.

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Abstract

Disruptions in the B cell differentiation process leading to translocations and mutations partly explain the development of Non-Hodgkin lymphomas (NHL). Recently, epigenetic mechanisms were also found to play an important role in NHL, including cytosine methylation, histone modifications and chromatin remodeling. Several of these processes were observed to be deregulation in lymphoma cells due to alterations (mutations or changed expression) in the enzymes involved. This essay gives an overview of the epigenetic modifiers that have been reported to be involved in NHL. Changes in the function or expression of TET2, DNMT3b, MLL2, EZH2, BMI1, JAK2, CBP/P300, ARID1A and BRG1 have been found in NHL cells. Functional studies indicated that these alterations change the expression of the target genes of the epigenetic modifiers, contributing to B cell malignancy. Most alterations affected histone modifications (MLL2 mutation, EZH2 mutation/overexpression, BMI1 deregulated expression, JAK2 amplification, CBP/P300 mutation). Mutated TET2 and overexpression of DNMT3b deregulated DNA methylation, and ARID1A and BRG1 mutations disrupted the functioning of chromatin remodeling complexes. Most mutations detected lead to a loss of function in the proteins, except for the mutation in EZH2, which resulted in enhanced activity. Overall, a lot of epigenetic modifiers involved in NHL have already been described, but more research is needed to identify all important epigenetic enzymes, their target genes and the interactions between the epigenetic mechanisms. Ultimately, this knowledge can be used for diagnostic and therapeutic purposes.

Item Type: Thesis (Master's Thesis / Essay)
Degree programme: Biology
Thesis type: Master's Thesis / Essay
Language: English
Date Deposited: 15 Feb 2018 07:53
Last Modified: 15 Feb 2018 07:53
URI: http://fse.studenttheses.ub.rug.nl/id/eprint/11149

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