Frequent dysregulation of the c-maf proto-oncogene at 16q23 by translocation to an Ig locus in multiple myeloma

Marta Chesi, P. Leif Bergsagel, Oluwatoyin O. Shonukan, Maria Luisa Martelli, Leslie A. Brents, Theresa Chen, Evelin Schröck, Thomas Ried, W. Michael Kuehl

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339 Scopus citations

Abstract

Dysregulation of oncogenes by translocation to an IgH (14q32) or IgL (κ, 2p11 or λ, 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. This is a US government work. There are no restrictions on its use.

Original languageEnglish (US)
Pages (from-to)4457-4463
Number of pages7
JournalBlood
Volume91
Issue number12
DOIs
StatePublished - Jun 15 1998

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Chesi, M., Bergsagel, P. L., Shonukan, O. O., Martelli, M. L., Brents, L. A., Chen, T., Schröck, E., Ried, T., & Kuehl, W. M. (1998). Frequent dysregulation of the c-maf proto-oncogene at 16q23 by translocation to an Ig locus in multiple myeloma. Blood, 91(12), 4457-4463. https://doi.org/10.1182/blood.v91.12.4457