Recent technology advances in genomic analysis have unraveled the genomic complexity and evolutionary process of multiple myeloma (MM). Hyperdiploidy or IgH translocations t (4;14), t (11;14), t (6;14), t (14;16), and t (14;20), leading to ectopic overexpression of MMSET/FGFR3, CCND1, CCND3, MAF, and MAFB, respectively, are initiating events. Subsequent secondary events, such as gene copy number alterations, and gene somatic mutations, participate in tumor progression in a branching pattern consistent with Darwin's evolutionary model. Copy number alterations, such as 1q21 amplification and del (17p), have been associated with adverse outcomes. N/KRAS mutations are most commonly found in around 20% of patients, but numerous gene mutations are infrequent. Pathological and clinical relevance of gene mutations combined with cytogenetic abnormalities are currently under investigation. Additionally, detailed genomic analysis of individual patients using targeted-sequencing panels has been facilitated, and efforts toward personalized therapy based on molecular features have begun. This paper outlines MM molecular pathology and its clinical application in Japanese patients.
Keywords: FISH; Molecular pathology; Multiple myeloma; Next-generation sequencing.