Multiple Myeloma

Multiple myeloma (MM) is a malignancy of plasma cells characterized by complex genetic abnormalities. Key alterations include losses and gains of chromosomal material. Loss of the tumor suppressor CDKN2C on chromosome 1p promotes unchecked cell proliferation, while amplification of CKS1B on chromosome 1q contributes to genomic instability.¹ Disease-initiating translocations involving the IGH locus, present in about 40% of cases, result in overexpression of partner genes due to IGH enhancer activity. Deletions of chromosome 13q, which often involve the tumor suppressors RB1 and LAMP1, are among the most frequent abnormalities in MM.

Hyperdiploid multiple myeloma (H-MM), observed in 50–60% of patients, is characterized by trisomies of odd-numbered chromosomes, such as 3, 5, 7, and 19.4 In contrast, deletions of TP53 on chromosome 17p, found in approximately 10% of newly diagnosed cases, result in the loss of a key tumor suppressor, leading to poor prognosis. These alterations highlight the diverse genetic landscape of MM and its influence on disease progression and treatment responses.