Multiple myeloma is a malignant proliferation of monoclonal plasma cells leading to clinical features that include hypercalcaemia,\nrenal dysfunction, anaemia, and bone disease (frequently referred to by the acronym CRAB) which represent evidence of end organ\nfailure. Recent evidence has revealed myeloma to be a highly heterogeneous disease composed of multiple molecularly-defined\nsubtypes each with varying clinicopathological features and disease outcomes. The major division within myeloma is between\nhyperdiploid and nonhyperdiploid subtypes. In this division, hyperdiploid myeloma is characterised by trisomies of certain odd\nnumbered chromosomes, namely, 3, 5, 7, 9, 11, 15, 19, and 21 whereas nonhyperdiploid myeloma is characterised by translocations\nof the immunoglobulin heavy chain alleles at chromosome 14q32 with various partner chromosomes, the most important of\nwhich being 4, 6, 11, 16, and 20. Hyperdiploid and nonhyperdiploid changes appear to represent early or even initiating mutagenic\nevents that are subsequently followed by secondary aberrations including copy number abnormalities, additional translocations,\nmutations, and epigenetic modifications which lead to plasma cell immortalisation and disease progression. The following review\nprovides a comprehensive coverage of the genetic and epigenetic events contributing to the initiation and progression of multiple\nmyeloma and where possible these abnormalities have been linked to disease prognosis.
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