Frequent dysregulation of the c-maf proto-oncogene at 16q23 by translocation to an Ig locus in multiple myeloma.
Dysregulation of oncogenes by translocation to an IgH (14q32) or IgL (kappa, 2p11 or lambda, 22q11) locus is a frequent event in the pathogenesis of B-cell tumors. Translocations involving an IgH locus and a diverse but nonrandom array of chromosomal loci occur in most multiple myeloma (MM) tumors even though the translocations often are not detected by conventional cytogenetic analysis. In a continuing analysis of translocations in 21 MM lines, we show that the novel, karyotypically silent t(14;16)(q32.3;q23) translocation is present in 5 MM lines, with cloned breakpoints from 4 lines dispersed over an approximately 500-kb region centromeric to the c-maf proto-oncogene at 16q23. Another line has a t(16;22)(q23;q11), with the breakpoint telomeric to c-maf, so that the translocation breakpoints in these 6 lines bracket c-maf. Only these 6 lines overexpress c-maf mRNA. As predicted for dysregulation of c-maf by translocation, there is selective expression of one c-maf allele in 2 informative lines with translocations. This is the first human tumor in which the basic zipper c-maf transcription factor is shown to function as an oncogene.
Chesi
M
M
Genetics Department, Medicine Branch, National Cancer Institute, Bethesda, MD, USA.
Bergsagel
P L
PL
Shonukan
O O
OO
Martelli
M L
ML
Brents
L A
LA
Chen
T
T
Schröck
E
E
Ried
T
T
Kuehl
W M
WM
D000595:Amino Acid Sequence; D018244:Chromosomes, Artificial, Yeast; D002883:Chromosomes, Human, Pair 14; D002885:Chromosomes, Human, Pair 16; D004268:DNA-Binding Proteins / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D005803:Genes, Immunoglobulin; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D017404:In Situ Hybridization, Fluorescence; D008969:Molecular Sequence Data; D009101:Multiple Myeloma / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051257:Proto-Oncogene Proteins c-maf; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D007143:Immunoglobulin Heavy Chains; C495607:MAF protein, human; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D051257:Proto-Oncogene Proteins c-maf