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Early Genetic Events Provide the Basis for a Clinical Classification of Multiple Myeloma

Correspondence: Mike Kuehl, 8901 Rockville Pike, Bldg. 8, Rm 5101, Bethesda, MD 20889 wmk{at}helix.nih.gov Leif Bergsagel, Mayo Clinic,13400 E. Shea Blvd., Scottsdale, AZ 85259; Phone (480) 301-4704, Fax (480) 301-7017, bergsagel.leif{at}mayo.edu

Abstract

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.

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