Molecular basis of multiple myeloma.

Abstract

Multiple myeloma (MM) is aheterogeneous hematological malignancy characterized by clonal expansion of malignant plasma cells in the bone marrow. The disease is accompanied by various clinical manifestations, such as bone lesions, anemia, hypercalcemia, and renal insufficiency. However, despite significant advances in treatment over the last two decades, the disease remains challenging to treat, and most patients relapse. Although its pathogenesis has not yet been elucidated, it is clear that genomic instability plays akey role in its develop-ment or resistance to treatment. In some instances, the cause of this instability is chromothripsis, aform of complex genomic rearrangement that involves shattering and subsequent haphazard reassembly of chromosomes within asingle catastrophic event. The resulting rearrangements involve avariety of structural changes, including deletions, duplications, inversions, and translocations, that lead to genome disruption. Specifically, these changes may result in alteration or inactivation of tumor suppressor genes (TP53and CDKN2C), activation of oncogenes (MAF, FGFR3, and CCND1) or genes involved in key cellular processes. Unraveling the mechanisms that result in chromothripsis provides opportunities to identify critical genes and pathways involved in MM pathogenesis. These findings may serve as abasis for improved dia-gnostic approaches. The goal of this review is to summarize the common primary and secondary chromosomal aberrations in MM with a particular focus on introducing complex chromosomal aberrations, especially chromothripsis in MM.