Multiple myeloma (MM) is a malignant neoplasm of terminally differentiated immunoglobulin-producing B lymphocytes called plasma cells. MM is the second most common hematologic malignancy, and it poses a heavy economic and social burden because it remains incurable and confers a profound disability to patients. Despite current progress in MM treatment, the disease invariably recurs, even after the transplantation of autologous hematopoietic stem cells (ASCT). Biological processes leading to a pathological myeloma clone and the mechanisms of further evolution of the disease are far from complete understanding. Genetically, MM is a complex disease that demonstrates a high level of heterogeneity. Myeloma genomes carry numerous genetic changes, including structural genome variations and chromosomal gains and losses, and these changes occur in combinations with point mutations affecting various cellular pathways, including genome maintenance. MM genome instability in its extreme is manifested in mutation kataegis and complex genomic rearrangements: chromothripsis, templated insertions, and chromoplexy. Chemotherapeutic agents used to treat MM add another level of complexity because many of them exacerbate genome instability. Genome abnormalities are driver events and deciphering their mechanisms will help understand the causes of MM and play a pivotal role in developing new therapies.

Cytosine deaminases of the AID/APOBEC family have a weighty influence on human health. These enzymes are part of the innate and humoral immunity; they participate in lipid metabolism and muscle development, protect cells from viruses and regulate retrotransposition. If the activity of AID/APOBEC deaminases is misregulated, they can become "weapons of mass destruction," causing deaminations in unprotected single-stranded DNA regions leading to genome-wide mutagenesis. Ultimately, mutations contribute to cell malignancy and rapid evolution of cancer cells, helping them to evade the organism's defense. Also, hypermutable tumor cells develop resistance to anti-cancer drugs. Here we overview current understanding of the structure, functions, and regulation of AID/APOBEC cytosine deaminases in connection to carcinogenesis.