|
|
 Previous Article | Table of Contents | Next Article 
Blood, 1 July 2001, Vol. 98, No. 1, pp. 217-223
NEOPLASIA
Cyclin D3 at 6p21 is dysregulated by recurrent
chromosomal translocations to immunoglobulin loci in
multiple myeloma
John Shaughnessy Jr,
Ana Gabrea,
Ying Qi,
Leslie Brents,
Fenghaung Zhan,
Erming Tian,
Jeffrey Sawyer,
Bart Barlogie,
P. Leif Bergsagel, and
Michael Kuehl
From the Donna D. and Donald M. Lambert Laboratory of
Myeloma Genetics and Myeloma and the Transplantation Research Center,
Arkansas Cancer Research Center, University of Arkansas for Medical
Sciences, Little Rock; the Genetics Department, Medicine Branch,
National Cancer Institute, Bethesda, MD; the Department of Medicine,
Division of Hematology and Oncology, Cornell University Medical
College, New York, NY.
Reciprocal chromosomal translocations, which are mediated by errors
in immunoglobulin heavy chain (IgH) switch recombination or somatic
hypermutation as plasma cells are generated in germinal centers, are
present in most multiple myeloma (MM) tumors. These translocations
dysregulate an oncogene that is repositioned in proximity to a strong
IgH enhancer. There is a promiscuous array of nonrandom chromosomal
partners (and oncogenes), with the 3 most frequent partners (11q13
[cyclin D1]; 4p16 [FGFR3 and MMSET]; 16q23 [c-maf])
involved in nearly half of MM tumors. It is now shown that a novel
t(6;14)(p21;q32) translocation is present in 1 of 30 MM cell lines and
that this cell line uniquely overexpresses cyclin D3. The cloned
breakpoint juxtaposes gamma 4 switch sequences with 6p21
sequences that are located about 65 kb centromeric to the cyclin
D3 gene. By metaphase chromosome analysis, the
t(6;14) (p21;q32) translocation was identified in 6 of 150 (4%)
primary MM tumors. Overexpression of cyclin D3 messenger RNA
(mRNA) was identified by microarray RNA expression analysis in
3 of 53 additional primary MM tumors, each of which was found to have a
t(6;14) translocation breakpoint by interphase fluorescence in
situ hybridization analysis. One tumor has a t(6;22)(p21;q11)
translocation, so that cyclin D3 is bracketed by the IgL and IgH
breakpoints. These results provide the first clear evidence for primary
dysregulation of cyclin D3 during tumorigenesis. It is suggested that
the initial oncogenic event for most MM tumors is a primary
immunoglobulin translocation that dysregulates cyclin D1, cyclin D3,
and other oncogenes to provide a proliferative stimulus to postgerminal center plasma cells.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
I. Joshi, L. M. Minter, J. Telfer, R. M. Demarest, A. J. Capobianco, J. C. Aster, P. Sicinski, A. Fauq, T. E. Golde, and B. A. Osborne
Notch signaling mediates G1/S cell-cycle progression in T cells via cyclin D3 and its dependent kinases
Blood,
February 19, 2009;
113(8):
1689 - 1698.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Wlodarska, D. Dierickx, V. Vanhentenrijk, K. Van Roosbroeck, H. Pospisilova, F. Minnei, G. Verhoef, J. Thomas, P. Vandenberghe, and C. De Wolf-Peeters
Translocations targeting CCND2, CCND3, and MYCN do occur in t(11;14)-negative mantle cell lymphomas
Blood,
June 15, 2008;
111(12):
5683 - 5690.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Bink, E. Haralambieva, M. Kremer, G. Ott, C. Beham-Schmid, L. de Leval, S. C. Peh, H. R. Laeng, U. Jutting, P. Hutzler, et al.
Primary extramedullary plasmacytoma: similarities with and differences from multiple myeloma revealed by interphase cytogenetics
Haematologica,
April 1, 2008;
93(4):
623 - 626.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Gonzalez, M. van der Burg, R. Garcia-Sanz, J. A. Fenton, A. W. Langerak, M. Gonzalez, J. J. M. van Dongen, J. F. San Miguel, and G. J. Morgan
Immunoglobulin gene rearrangements and the pathogenesis of multiple myeloma
Blood,
November 1, 2007;
110(9):
3112 - 3121.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Dispenzieri, S. V. Rajkumar, M. A. Gertz, M. Q. Lacy, R. A. Kyle, P. R. Greipp, T. E. Witzig, J. A. Lust, S. J. Russell, S. R. Hayman, et al.
Treatment of Newly Diagnosed Multiple Myeloma Based on Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART): Consensus Statement
Mayo Clin. Proc.,
March 1, 2007;
82(3):
323 - 341.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. B. Baughn, M. Di Liberto, K. Wu, P. L. Toogood, T. Louie, R. Gottschalk, R. Niesvizky, H. Cho, S. Ely, M. A.S. Moore, et al.
A novel orally active small molecule potently induces g1 arrest in primary myeloma cells and prevents tumor growth by specific inhibition of cyclin-dependent kinase 4/6.
Cancer Res.,
August 1, 2006;
66(15):
7661 - 7667.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Ely, M. Di Liberto, R. Niesvizky, L. B. Baughn, H. J. Cho, E. N. Hatada, D. M. Knowles, J. Lane, and S. Chen-Kiang
Mutually Exclusive Cyclin-Dependent Kinase 4/Cyclin D1 and Cyclin-Dependent Kinase 6/Cyclin D2 Pairing Inactivates Retinoblastoma Protein and Promotes Cell Cycle Dysregulation in Multiple Myeloma
Cancer Res.,
December 15, 2005;
65(24):
11345 - 11353.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Agnelli, S. Bicciato, M. Mattioli, S. Fabris, D. Intini, D. Verdelli, L. Baldini, F. Morabito, V. Callea, L. Lombardi, et al.
Molecular Classification of Multiple Myeloma: A Distinct Transcriptional Profile Characterizes Patients Expressing CCND1 and Negative for 14q32 Translocations
J. Clin. Oncol.,
October 10, 2005;
23(29):
7296 - 7306.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Jaksic, S. Trudel, H. Chang, Y. Trieu, X. Qi, J. Mikhael, D. Reece, C. Chen, and A. K. Stewart
Clinical Outcomes in t(4;14) Multiple Myeloma: A Chemotherapy-Sensitive Disease Characterized by Rapid Relapse and Alkylating Agent Resistance
J. Clin. Oncol.,
October 1, 2005;
23(28):
7069 - 7073.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. L. Bergsagel and W. M. Kuehl
Molecular Pathogenesis and a Consequent Classification of Multiple Myeloma
J. Clin. Oncol.,
September 10, 2005;
23(26):
6333 - 6338.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Pruneri, L. Pignataro, S. Valentini, S. Fabris, P. Maisonneuve, N. Carboni, S. Pece, M. Capra, B. Del Curto, A. Neri, et al.
Cyclin D3 Immunoreactivity Is an Independent Predictor of Survival in Laryngeal Squamous Cell Carcinoma
Clin. Cancer Res.,
January 1, 2005;
11(1):
242 - 248.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Song, J. Cooperman, D. L. Letting, G. A. Blobel, and J. K. Choi
Identification of Cyclin D3 as a Direct Target of E2A Using DamID
Mol. Cell. Biol.,
October 1, 2004;
24(19):
8790 - 8802.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Hideshima, P. L. Bergsagel, W. M. Kuehl, and K. C. Anderson
Advances in biology of multiple myeloma: clinical applications
Blood,
August 1, 2004;
104(3):
607 - 618.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Fonseca, B. Barlogie, R. Bataille, C. Bastard, P. L. Bergsagel, M. Chesi, F. E. Davies, J. Drach, P. R. Greipp, I. R. Kirsch, et al.
Genetics and Cytogenetics of Multiple Myeloma: A Workshop Report
Cancer Res.,
February 15, 2004;
64(4):
1546 - 1558.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.-L. Harousseau, J. Shaughnessy Jr., and P. Richardson
Multiple Myeloma
Hematology,
January 1, 2004;
2004(1):
237 - 256.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Shaughnessy Jr
Primer on Medical Genomics Part IX: Scientific and Clinical Applications of DNA Microarrays--Multiple Myeloma as a Disease Model
Mayo Clin. Proc.,
September 1, 2003;
78(9):
1098 - 1109.
[Abstract]
[PDF]
|
|
|
|
|
|
|
M. Santra, F. Zhan, E. Tian, B. Barlogie, and J. Shaughnessy Jr
A subset of multiple myeloma harboring the t(4;14)(p16;q32) translocation lacks FGFR3 expression but maintains an IGH/MMSET fusion transcript
Blood,
March 15, 2003;
101(6):
2374 - 2376.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. J. Keats, T. Reiman, C. A. Maxwell, B. J. Taylor, L. M. Larratt, M. J. Mant, A. R. Belch, and L. M. Pilarski
In multiple myeloma, t(4;14)(p16;q32) is an adverse prognostic factor irrespective of FGFR3 expression
Blood,
February 15, 2003;
101(4):
1520 - 1529.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Barille-Nion, B. Barlogie, R. Bataille, P. L. Bergsagel, J. Epstein, R. G. Fenton, J. Jacobson, W. M. Kuehl, J. Shaughnessy, and G. Tricot
Advances in Biology and Therapy of Multiple Myeloma
Hematology,
January 1, 2003;
2003(1):
248 - 278.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. O. Claudio, E. Masih-Khan, H. Tang, J. Goncalves, M. Voralia, Z. H. Li, V. Nadeem, E. Cukerman, O. Francisco-Pabalan, C. C. Liew, et al.
A molecular compendium of genes expressed in multiple myeloma
Blood,
August 28, 2002;
100(6):
2175 - 2186.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Moreau, T. Facon, X. Leleu, N. Morineau, P. Huyghe, J.-L. Harousseau, R. Bataille, and H. Avet-Loiseau
Recurrent 14q32 translocations determine the prognosis of multiple myeloma, especially in patients receiving intensive chemotherapy
Blood,
August 13, 2002;
100(5):
1579 - 1583.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. C. Anderson, J. D. Shaughnessy Jr., B. Barlogie, J.-L. Harousseau, and G. D. Roodman
Multiple Myeloma
Hematology,
January 1, 2002;
2002(1):
214 - 240.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
T. Sonoki, L. Harder, D. E. Horsman, L. Karran, I. Taniguchi, T. G. Willis, S. Gesk, D. Steinemann, E. Zucca, B. Schlegelberger, et al.
Cyclin D3 is a target gene of t(6;14)(p21.1;q32.3) of mature B-cell malignancies
Blood,
November 1, 2001;
98(9):
2837 - 2844.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. S. Dalton, P. L. Bergsagel, W. M. Kuehl, K. C. Anderson, and J. L. Harousseau
Multiple Myeloma
Hematology,
January 1, 2001;
2001(1):
157 - 177.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
