IgH Translocations in Multiple Myeloma: A Nearly Universal Event that Rarely Involves c-myc

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Abstract
Dysregulation of c-myc by translocation to the switch regions of the IgH locus occurs in most murine plasmacytomas. Translocations involving 14q32 have been reported in 20–40% of abnormal karyotypes from human multiple myeloma (MM), and involve a variety of loci. Using cytogenetics, FISH and a Southern blot assay, we analyzed 21 MM cell lines and one plasma cell leukemia and identified evidence of a 14q32 translocation in 20/22 samples. The partner loci involved are 11q13 in 6 (associated with cyc lin D1 expression), 4p16 in 6 (associated with FGFR3 expression), unidentified in 3 and lpl3, 6, 8q24, 12q24, 16q23, and 21q22 once each. We conclude that conventional karyotypes underestimate the frequency of 14q32 translocations in MM, where they appear to be a nearly universal event. The translocations most frequently involve IgH switch regions, and include two recurrent partner loci (1 lql3 and 4pl6) and a promiscuous array of other partner loci. Although c-myc appears to be cis-dysregulated frequently in MM, it is only rarely translocated to the IgH locus.