- Defining risk factors for genomic instability in B cells: Novel insights from NGS-based technologies
- Award date
- 26 November 2013
- Number of pages
- Document type
- PhD thesis
- Faculty of Science (FNWI)
- Swammerdam Institute for Life Sciences (SILS)
Cancer is caused by an accumulation of somatic DNA mutations. Knowledge on the cause and consequence of these mutations is essential for an effective prevention, diagnosis, prognosis and treatment of cancer. Our research focused on B cell non-Hodgkin lymphomas. These lymphomas are derived from germinal centers. Germinal centers are defined histological structures that develop during an immune response in secondary lymphatic tissues such as of lymph nodes, spleens or Peyer's Patches. Within the germinal center, B cells activated by cognate antigen undergo a critical development phase which a DNA mutator system is turned on in order to mutate antibody-encoding genes with an extremely high frequency. While this intentional mutagenesis process is of great importance for an effective immune response, it brings great risks. Disruption or aberrant targeting of this mutagenesis system may lead to genetic instability and the development of B-cell lymphomas. By investigating DNA binding profiles of activation-induced cytidine deaminase (AID), a protein central in this mutagenesis process, we aimed to answer the following questions: How specific is the mutagenesis process targeted throughout the genome? Which (onco)genes are unintentionally mutated by AID? How does AID contribute to genetic instability and especially chromosomal translocations? Chromosomal translocations are genomic mutations that occur when a DNA segment is moved from one chromosome to another (or within a chromosome). This genomic aberration can lead to deregulation of specific genes characteristic for well-defined B cell non-Hodgkin lymphomas.
- Research conducted at: Universiteit van Amsterdam
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