IgH translocations in multiple myeloma: a nearly universal event that rarely involves c-myc.
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 cells 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 cyclin D1 expression), 4p16 in 6 (associated with FGFR3 expression), unidentified in 3 and 1p13, 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 (11q13 and 4p16) 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.
Bergsagel
P L
PL
Cornell University Medical College, New York, NY 10021, USA.
Nardini
E
E
Brents
L
L
Chesi
M
M
Kuehl
W M
WM
D000818:Animals; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D005803:Genes, Immunoglobulin; D016259:Genes, myc; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007134:Immunoglobulin Switch Region / Q000235:genetics; D051379:Mice; D009101:Multiple Myeloma / Q000235:genetics* / Q000276:immunology*; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
D007143:Immunoglobulin Heavy Chains