FREQUENT DYSREGULATION OF THE C-MAF PROTOONCOGENE 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 pathoge nesis of B-cell tumors. Translocations involving an IgH locus and a di verse but nonrandom array of chromosomal loci occur in most multiple m yeloma (MM) tumors even though the translocations often are not detect ed by conventional cytogenetic analysis. In a continuing analysis of t ranslocations in 21 MM lines, we show that the novel, karyotypically s ilent t(14;16)(q32.3;q23) translocation is present in 5 MM lines, with cloned breakpoints from 4 lines dispersed over an approximately 500-k b region centromeric to the c-maf proto oncogene at 16q23. Another lin e 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. Onl y 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 sh own to function as an oncogene.