Early genetic events provide the basis for a clinical classification of multiple myeloma.
Multiple myeloma is a tumor of somatically mutated, isotype-switched plasma cells that accumulate in the bone marrow leading to bone destruction and bone marrow failure. The germinal center processes of somatic hypermutation and switch recombination are implicated in the development of recurrent immunoglobulin gene translocations in 40% of patients. These affect five loci: 11q13, 6p21, 4p16, 16q23 and 20q11, leading to dysregulation of CCND1, CCND2, FGFR3/MMSET, c-MAF and MAFB respectively. The remaining 60% of patients can be divided into four groups based on their expression of CCND1 and CCND2. The largest group (40%) ectopically express CCND1 bi-allelically and have hyperdiploidy with multiple trisomies of chromosomes 3, 5, 7, 9, 11, 15, 19 and 21. The translocation and cyclin D (TC) groups identify patients with different genetics, biology, clinical features, prognosis and response to therapy.
Kuehl
W Michael
WM
National Cancer Institute, Bethesda, MD 20889, USA. bergsagel.leif@mayo.edu
Bergsagel
P Leif
PL
D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002882:Chromosomes, Human, Pair 13; D019938:Cyclin D1 / Q000235:genetics; D056742:Cyclin D2; D016213:Cyclins / Q000235:genetics; D004171:Diploidy; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D051258:MafB Transcription Factor / Q000235:genetics; D008875:Middle Aged; D008998:Monoclonal Gammopathy of Undetermined Significance / Q000235:genetics / Q000276:immunology; D009101:Multiple Myeloma / Q000145:classification / Q000235:genetics*; D010265:Paraproteinemias / Q000453:epidemiology / Q000235:genetics; D051257:Proto-Oncogene Proteins c-maf / Q000235:genetics; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics; D012008:Recurrence; D014178:Translocation, Genetic; D014314:Trisomy
C530104:CCND1 protein, human; C080336:CCND2 protein, human; D056742:Cyclin D2; D016213:Cyclins; D007143:Immunoglobulin Heavy Chains; C495607:MAF protein, human; C490407:MAFB protein, human; D051258:MafB Transcription Factor; D051257:Proto-Oncogene Proteins c-maf; D019938:Cyclin D1; C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3