Aberrant patterns of DNA methylation in B cell lymphoma

Stoffers, A.E. (2014) Aberrant patterns of DNA methylation in B cell lymphoma. Bachelor's Thesis, Biology.

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Abstract

During B-cell maturation genetic and epigenetic changes can occur that facilitate the development of B-cell lymphoma. Among the epigenetic changes there is DNA methylation, hypermethylation of the tumor suppressor genes(TSGs) by DNA methyltransferases(DNMTs) can be a factor in the development of B cell lymphoma. There are different types of B-cell lymphoma and this review focusses on Burkitt lymphoma (BL), Follicular lymphoma(FL) and Diffuse large B cell lymphoma(DLBCL). In these B-cell lymphomas we analyse which TSGs are hypermethylated, what the roles of these TSGs are in tumor development/maintenance, and what the possible epigenetic therapies to de-methylate the hypermethylated TSGs are. The promoter of BIM, DAPK, P16, DSP, and DLC-1 are hypermethylated in BL, FL and DLBCL. Inactivation of these genes causes poorer overall survival and disease freesurvival. However these genes are not hypermethylated in all the patients. The application of epigenetic therapies to cause re expression of the TSGs is promising. Especially nucleoside analogues, which trap the DNMTs are promising. Also gene upregulating effects have been found of these drugs on P16, DAPK and BIM. The other type of epigenetic therapy is the non-nucleoside analogues, that block the DNMT enzymes. It is not known yet if these drugs have an upregulating effect on the genes studied in this review. These findings conclude that the TSGs BIM, DAPK, P16, DSP, and DLC-1 are hypermethylated in a part of the patients with B-cell lymphoma. With epigenetic therapies these genes can be reactivated and this has a positive effect on the overall survival of the patients with hypermethylation of these genes. However with the epigenetic therapies it is important to notice that not only the TSGs become hypomethylated, this could also happen to the oncogenes, so it is important for development of a good epigenetic therapy that it only reactivates the aberrant silenced genes.

Item Type:	Thesis (Bachelor's Thesis)
Degree programme:	Biology
Thesis type:	Bachelor's Thesis
Language:	English
Date Deposited:	15 Feb 2018 07:57
Last Modified:	15 Feb 2018 07:57
URI:	https://fse.studenttheses.ub.rug.nl/id/eprint/11781

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