Advertisement

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

  • P. L. Bergsagel
  • E. Nardini
  • L. Brents
  • M. Chesi
  • W. M. Kuehl
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 224)

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.

Keywords

Multiple Myeloma None None Partner Locus Switch Region Translocation Breakpoint 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Potter M, Wiener F (1992) Plasmacytomagenesis in mice: model of neoplastic development dependent upon chromosomal translocations. Carcinogenesis 13:1681–97PubMedCrossRefGoogle Scholar
  2. 2.
    Kuehl WM, Brents LA, Chesi M, Huppi K, Bergsagel PL (1997) Dysregulation of c-myc in multiple myeloma. Curr Top Microbiol ImmunolGoogle Scholar
  3. 3.
    Kuehl WM, Brents LA, Chesi M, Bergsagel PL (1996) Selective expression of one c-myc allele in two human myeloma cell lines. Cancer Res 56:4370–4373PubMedGoogle Scholar
  4. 4.
    Lai JL, Zandecki M, Mary JY, Bernardi F, Izydorczyk V, Flactif M, Morel P, Jouet JP, Bauters F, Facon T (1995) Improved cytogenetics in multiple-myeloma — a study of 151 patients including 117 patients at diagnosis. Blood 85:2490–2497PubMedGoogle Scholar
  5. 5.
    Sawyer JR, Waldron JA, Jagannath S, Barlogie B (1995) Cytogenetic findings in 200 patients with multiple-myeloma. Cancer Gen Cytogen 82:41–49CrossRefGoogle Scholar
  6. 6.
    Bergsagel PL, Chesi M, Nardini E, Brents LA, Kirby SL, Kuehl WM (1996) Promiscuous translocations into IgH switch regions in multiple myeloma. Proc Natl Acad Sci USA 93:13931–13936PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Chesi M, Bergsagel PL, Brents LA, Smith CA, Gerhard DS, Kuehl WM (1996) Dysregulation of cyclin D1 by translocation into an IgH gamma switch region in two multiple myeloma cell lines. Blood 88:674–681PubMedGoogle Scholar
  8. 8.
    Chesi M, Nardini E, Schrock E, Ried T, Brents LA, Kuehl WM, Bergsagel PL (1997) Frequent dysregulation of fibroblast growth factor receptor 3 by t(4;14)(p16.3;q32.3) translocation in multiple myeloma, submittedGoogle Scholar
  9. 9.
    Taniwaki M, Nishida K, Takashima T, Nakagawa H, Fujii H, Tamaki T, Shimazaki C, Horiike S, Misawa S, Abe T, et a (1994) Nonrandom chromosomal rearrangements of 14q32.3 and 19p13.3 and preferential deletion of 1p in 21 patients with multiple myeloma and plasma cell leukemia. Blood 84:2283–90PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1997

Authors and Affiliations

  • P. L. Bergsagel
    • 1
  • E. Nardini
    • 1
  • L. Brents
    • 2
  • M. Chesi
    • 2
  • W. M. Kuehl
    • 2
  1. 1.Cornell University Medical CollegeNew YorkUSA
  2. 2.NCI-Navy Medical Oncology BranchBethesdaUSA

Personalised recommendations