Genetic Predispositions for Multiple Myeloma

Some of the most important prognostic factors in multiple myeloma are determined by cytogenetics.
These factors are typically assessed in two ways: by karyotype analysis and by fluorescence in situ hybridization (FISH).
Karyotyping can be performed to reveal the ploidy status of myeloma cells and whether there have been any substantial chromosomal gains or losses.
More than half of all myeloma patients have hyperdiploid karyotypes with chromosome numbers ranging between 48 and 74. These patients tend to have a favorable prognosis, although there are some exceptions. Patients with losses of chromosome 13, for example, typically have a worse prognosis. By comparison, FISH is used to detect specific chromosomal translocations.
Most non-hyperdiploid patients have translocations between the strong immunoglobulin enhancer of the IgH locus and one of several common oncogenes, resulting in their overexpression.
Specifically, non-random early-onset translocations of the IgH enhancer are frequently observed to be juxtaposed with c-MAF, cyclin D1, cyclin D3, FGFR3 and MMSET, and MAFB.
The prognostic outcome of a patient depends then on the specific translocation present.
Ultimately, those patients who are identified as belonging to a poor prognostic subpopulation are typically administered more aggressive treatment.