Epigenetic Events

An epigenetic event is defined as a genetic modification without alterations of DNA nucleotide sequences. Hypermethylation is an epigenetic event that is frequently associated with myeloma. It leads to the inac-tivation of genes, including death-associated protein kinase (DAPK), SOCS1, p15, and p16.

Hypermethylation of p15 and p16 was observed in 75 and 67% of one group of myeloma patients, respec-tively.67 Hypermethylation of p15 and p16 was associated with blastic disease in myeloma, and may be causally related to plasmacytoma development.67 Hypermethylation of p16 was also shown to correlate with an increased proliferative rate of plasma cells, shorter survival, and poor outcome, albeit not as an independent prognostic factor.68 In MGUS, the frequencies of p15 and p16 hypermethylation were similar to myeloma patients, suggesting an early genetic change rather than a late transformation event.69

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