Genetics of multiple myeloma

Multiple myeloma (MM) is a heterogeneous disease that utilizes genetic aberrations of the clonal plasma cells as one method to define its major subtypes. While specific genetic changes do not contribute to the definition of the diagnosis of MM, these changes have prognostic significance that allows division into different risk groups and subsequently allows different treatment guidelines based on risk group. Drugs like the proteasome inhibitor bortezomib have shown promise in the treatment of the high-risk group, but further improved treatment options are needed to target this group with the worst prognosis. Currently, no marker or genetic alteration has a predictive value to treatment response, and research is ongoing to find such predictive markers which would be invaluable to determine treatment sequence or combination. Promising new studies are revealing the importance of microRNA abnormalities and epigenetic changes in MM. While FISH and cytogenetic analyses are the standard of genetic evaluation, they have significant limitations, and other methods, including gene expression analyses and genomic sequencing, are evolving and will likely replace current methods with time with improved sensitivity. This chapter intends to summarize critical genetic alterations in MM, review research with microRNA and epigenetic changes, and discuss upcoming methods for genomic analysis in MM.