Cells can become cancerous when gene regulation is disrupted. Factors affecting gene regulation include mutations in DNA sequence, nucleosome positioning, chromatin organization and epigenetic changes in DNA methylation and histone modifications. Numerous genetic mutations of inherited cancers have been identified, as there is a large body of research dedicated to identifying DNA mutations that are linked to tumor initiation. After initiation, tumor progression often occurs due to multiple additional dysregulation events, including epigenetic changes which are often not as easily identifiable as DNA mutations (Feinberg et al. 2004). Although epigenetic factors can also initiate tumors, this paper will focus on epigenetic changes that occur
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Hypermethylation of CGIs, in contrast, can cause silencing of tumor suppressors in a heritable manner. Histone acetylation and methylation, described above, function by altering chromatin structure and recruiting transcription factors to regulate gene expression. The following paragraphs consider the dysregulation of transcription involved in a specific cancer, multiple myeloma.
Multiple Myeloma
Multiple myeloma (MM) is a genetically complex disease that is increasingly diagnosed in the current ageing population. It is a cancer characterized by abnormal clonal plasma cells in the bone marrow (Morgan et al. 2012). B cells are a type of white blood cell that mature in the bone marrow, a subset of which differentiate into antibody-producing plasma cells, which are the type of cells that form the tumor in myeloma. During maturation, B cells undergo characteristic gene rearrangements and mutations known as V(D)J recombination, somatic hypermutation (SHM) and class-switch recombination (CSR) in the immunoglobulin (Ig) genes to generate diverse antibodies and function properly in the adaptive immune response. These rearrangements are frequently accompanied by chromosomal translocations because they are mediated by double strand
Hypermethylation of CGIs, in contrast, can cause silencing of tumor suppressors in a heritable manner. Histone acetylation and methylation, described above, function by altering chromatin structure and recruiting transcription factors to regulate gene expression. The following paragraphs consider the dysregulation of transcription involved in a specific cancer, multiple myeloma.
Multiple Myeloma
Multiple myeloma (MM) is a genetically complex disease that is increasingly diagnosed in the current ageing population. It is a cancer characterized by abnormal clonal plasma cells in the bone marrow (Morgan et al. 2012). B cells are a type of white blood cell that mature in the bone marrow, a subset of which differentiate into antibody-producing plasma cells, which are the type of cells that form the tumor in myeloma. During maturation, B cells undergo characteristic gene rearrangements and mutations known as V(D)J recombination, somatic hypermutation (SHM) and class-switch recombination (CSR) in the immunoglobulin (Ig) genes to generate diverse antibodies and function properly in the adaptive immune response. These rearrangements are frequently accompanied by chromosomal translocations because they are mediated by double strand