|
|
 Previous Article | Table of Contents | Next Article 
Blood, 15 March 2002, Vol. 99, No. 6, pp. 2185-2191
NEOPLASIA
Oncogenesis of multiple myeloma: 14q32 and 13q chromosomal
abnormalities are not randomly distributed, but correlate with natural
history, immunological features, and clinical presentation
Hervé Avet-Loiseau,
Thierry Facon,
Bernard Grosbois,
Florence Magrangeas,
Marie-José Rapp,
Jean-Luc Harousseau,
Stéphane Minvielle, and
Régis Bataille for the Intergroupe Francophone du
Myélome
From the Laboratory and Clinical Department of
Hematology, University Hospital, Nantes, France; Clinical Department of
Hematology, University Hospital, Lille, France; Department of Internal
Medicine, University Hospital, Rennes, France; and INSERM U463, Nantes,
France.
Multiple myeloma (MM) is a plasma-cell malignancy
characterized by marked epidemiological, biological, and clinical
heterogeneity. The goal of this study was to find a genetic basis for
this heterogeneity. Using fluorescence in situ hybridization, we
analyzed a prospective cohort of 901 patients with various plasma-cell
disorders monoclonal gammopathies of undetermined
significance, smoldering MM, MM, and primary plasma-cell
leukemiafor genetic abnormalities involving the 13q14 and 14q32
chromosomal regions; the patients were consecutively enrolled in the
Intergroupe Francophone du Myélome clinical trials, We performed
statistical analyses comparing these chromosomal abnormalities in
terms of immunological (ie, immunoglobulin types and
light-chain subtypes) and clinical status and, to some exent, prognostic features. It was found that 14q32 translocations and del(13)
are the most frequent chromosomal abnormalities, observed in 75% and
45% of the patients, respectively, and are not randomly distributed,
but interconnected. Second, correlations between them allowed us to
define 4 major genetic categories of patients: (1) patients lacking any
14q32 abnormality (25%) and generally also lacking del(13); (2)
patients presenting either t(4;14) or t(14;16), almost always
associated with a del(13) (15% of patients); (3) patients with other
14q32 abnormalities and presenting del(13) (25%); and (4) patients
with other 14q32 abnormalities but not presenting del(13)
(35%). Third, we show that this genetic stratification is
highly correlated with immunological status and clinical presentation and with some major prognostic factors. For the first time, this study
gives genetic support to the heterogeneity observed in patients with MM
and demontrates that the 14q32 and 13q chromosomal abnormalities are
not randomly distributed. The strong correlations we found might be the
basis for a novel genetic classification of MM, as has been previously
demonstrated for leukemias and lymphomas. Furthermore, our study
supports different models for MM oncogenesis.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
L. Chiecchio, G. P. Dagrada, R. K.M. Protheroe, D. M. Stockley, A. G. Smith, K. H. Orchard, N. C.P. Cross, C. J. Harrison, F. M. Ross, and on behalf of the UK Myeloma Forum
Loss of 1p and rearrangement of MYC are associated with progression of smouldering myeloma to myeloma: sequential analysis of a single case
Haematologica,
July 1, 2009;
94(7):
1024 - 1028.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.-L. Harousseau and P. Moreau
Autologous Hematopoietic Stem-Cell Transplantation for Multiple Myeloma
N. Engl. J. Med.,
June 18, 2009;
360(25):
2645 - 2654.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. H. Bryce, R. P. Ketterling, M. A. Gertz, M. Lacy, R. A. Knudson, S. Zeldenrust, S. Kumar, S. Hayman, F. Buadi, R. A. Kyle, et al.
Translocation t(11;14) and survival of patients with light chain (AL) amyloidosis
Haematologica,
March 1, 2009;
94(3):
380 - 386.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Bisping, D. Wenning, M. Kropff, D. Gustavus, C. Muller-Tidow, M. Stelljes, G. Munzert, F. Hilberg, G. J. Roth, M. Stefanic, et al.
Bortezomib, Dexamethasone, and Fibroblast Growth Factor Receptor 3-Specific Tyrosine Kinase Inhibitor in t(4;14) Myeloma
Clin. Cancer Res.,
January 15, 2009;
15(2):
520 - 531.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. Decaux, L. Lode, F. Magrangeas, C. Charbonnel, W. Gouraud, P. Jezequel, M. Attal, J.-L. Harousseau, P. Moreau, R. Bataille, et al.
Prediction of Survival in Multiple Myeloma Based on Gene Expression Profiles Reveals Cell Cycle and Chromosomal Instability Signatures in High-Risk Patients and Hyperdiploid Signatures in Low-Risk Patients: A Study of the Intergroupe Francophone du Myelome
J. Clin. Oncol.,
October 10, 2008;
26(29):
4798 - 4805.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Bochtler, U. Hegenbart, F. W. Cremer, C. Heiss, A. Benner, D. Hose, M. Moos, J. Bila, C. R. Bartram, A. D. Ho, et al.
Evaluation of the cytogenetic aberration pattern in amyloid light chain amyloidosis as compared with monoclonal gammopathy of undetermined significance reveals common pathways of karyotypic instability
Blood,
May 1, 2008;
111(9):
4700 - 4705.
[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]
|
|
|
|
|
|
|
X. Mao, A. K. Stewart, R. Hurren, A. Datti, X. Zhu, Y. Zhu, C. Shi, K. Lee, R. Tiedemann, Y. Eberhard, et al.
A chemical biology screen identifies glucocorticoids that regulate c-maf expression by increasing its proteasomal degradation through up-regulation of ubiquitin
Blood,
December 1, 2007;
110(12):
4047 - 4054.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Brousseau, X. Leleu, J. Gerard, T. Gastinne, A. Godon, F. Genevieve, M. Dib, J.-L. Lai, T. Facon, M. Zandecki, et al.
Hyperdiploidy Is a Common Finding in Monoclonal Gammopathy of Undetermined Significance and Monosomy 13 Is Restricted to These Hyperdiploid Patients
Clin. Cancer Res.,
October 15, 2007;
13(20):
6026 - 6031.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Tatetsu, S. Ueno, H. Hata, Y. Yamada, M. Takeya, H. Mitsuya, D. G. Tenen, and Y. Okuno
Down-regulation of PU.1 by Methylation of Distal Regulatory Elements and the Promoter Is Required for Myeloma Cell Growth
Cancer Res.,
June 1, 2007;
67(11):
5328 - 5336.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Mulligan, C. Mitsiades, B. Bryant, F. Zhan, W. J. Chng, S. Roels, E. Koenig, A. Fergus, Y. Huang, P. Richardson, et al.
Gene expression profiling and correlation with outcome in clinical trials of the proteasome inhibitor bortezomib
Blood,
April 15, 2007;
109(8):
3177 - 3188.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Avet-Loiseau, M. Attal, P. Moreau, C. Charbonnel, F. Garban, C. Hulin, S. Leyvraz, M. Michallet, I. Yakoub-Agha, L. Garderet, et al.
Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myelome
Blood,
April 15, 2007;
109(8):
3489 - 3495.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. R. Cook, M. Hartke, J. Pettay, and R. R. Tubbs
Fluorescence in Situ Hybridization Analysis of Immunoglobulin Heavy Chain Translocations in Plasma Cell Myeloma Using Intact Paraffin Sections and Simultaneous CD138 Immunofluorescence
J. Mol. Diagn.,
September 1, 2006;
8(4):
459 - 465.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. M. S. Muller, A. Geibel, H. P. H. Neumann, A. Kuhnemund, A. Schmitt-Graff, J. Bohm, and M. Engelhardt
Primary (AL) Amyloidosis in Plasma Cell Disorders
Oncologist,
July 1, 2006;
11(7):
824 - 830.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Cavo, C. Terragna, M. Renzulli, E. Zamagni, P. Tosi, N. Testoni, C. Nicci, D. Cangini, P. Tacchetti, T. Grafone, et al.
Poor Outcome With Front-Line Autologous Transplantation in t(4;14) Multiple Myeloma: Low Complete Remission Rate and Short Duration of Remission
J. Clin. Oncol.,
January 20, 2006;
24(3):
e4 - e5.
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. W. Dewald, T. Therneau, D. Larson, Y. K. Lee, S. Fink, S. Smoley, S. Paternoster, A. Adeyinka, R. Ketterling, D. L. Van Dyke, et al.
Relationship of patient survival and chromosome anomalies detected in metaphase and/or interphase cells at diagnosis of myeloma
Blood,
November 15, 2005;
106(10):
3553 - 3558.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. Chen, B. Issa, S. Huang, E. Aston, J. Xu, M. Yu, A. R. Brothman, and M. Glenn
A Practical Approach to the Detection of Prognostically Significant Genomic Aberrations in Multiple Myeloma
J. Mol. Diagn.,
November 1, 2005;
7(5):
560 - 565.
[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]
|
|
|
|
|
|
|
A. K. Stewart and R. Fonseca
Prognostic and Therapeutic Significance of Myeloma Genetics and Gene Expression Profiling
J. Clin. Oncol.,
September 10, 2005;
23(26):
6339 - 6344.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S.-Y. Huang, M. Yao, J.-L. Tang, W. Tsay, F.-Y. Lee, M.-C. Liu, C.-H. Wang, Y.-C. Chen, M.-C. Shen, and H.-F. Tien
Clinical significance of cytogenetics and interphase fluorescence in situ hybridization analysis in newly diagnosed multiple myeloma in Taiwan
Ann. Onc.,
September 1, 2005;
16(9):
1530 - 1538.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Moreaux, F. W. Cremer, T. Reme, M. Raab, K. Mahtouk, P. Kaukel, V. Pantesco, J. De Vos, E. Jourdan, A. Jauch, et al.
The level of TACI gene expression in myeloma cells is associated with a signature of microenvironment dependence versus a plasmablastic signature
Blood,
August 1, 2005;
106(3):
1021 - 1030.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. L. Bergsagel, W. M. Kuehl, F. Zhan, J. Sawyer, B. Barlogie, and J. Shaughnessy Jr
Cyclin D dysregulation: an early and unifying pathogenic event in multiple myeloma
Blood,
July 1, 2005;
106(1):
296 - 303.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Chang, A. K. Stewart, X. Y. Qi, Z. H. Li, Q. L. Yi, and S. Trudel
Immunohistochemistry accurately predicts FGFR3 aberrant expression and t(4;14) in multiple myeloma
Blood,
July 1, 2005;
106(1):
353 - 355.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Mateo, M. Castellanos, A. Rasillo, N. C. Gutierrez, Ma. A. Montalban, Ma. L. Martin, J. Ma. Hernandez, Ma. C. Lopez-Berges, L. Montejano, J. Blade, et al.
Genetic Abnormalities and Patterns of Antigenic Expression in Multiple Myeloma
Clin. Cancer Res.,
May 15, 2005;
11(10):
3661 - 3667.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. J. Keats, C. A. Maxwell, B. J. Taylor, M. J. Hendzel, M. Chesi, P. L. Bergsagel, L. M. Larratt, M. J. Mant, T. Reiman, A. R. Belch, et al.
Overexpression of transcripts originating from the MMSET locus characterizes all t(4;14)(p16;q32)-positive multiple myeloma patients
Blood,
May 15, 2005;
105(10):
4060 - 4069.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Trudel, Z. H. Li, E. Wei, M. Wiesmann, H. Chang, C. Chen, D. Reece, C. Heise, and A. K. Stewart
CHIR-258, a novel, multitargeted tyrosine kinase inhibitor for the potential treatment of t(4;14) multiple myeloma
Blood,
April 1, 2005;
105(7):
2941 - 2948.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. M. Kuehl and P. L. Bergsagel
Early Genetic Events Provide the Basis for a Clinical Classification of Multiple Myeloma
Hematology,
January 1, 2005;
2005(1):
346 - 352.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Rasmussen, M. Kuehl, M. Lodahl, H. E. Johnsen, and I. M. S. Dahl
Possible roles for activating RAS mutations in the MGUS to MM transition and in the intramedullary to extramedullary transition in some plasma cell tumors
Blood,
January 1, 2005;
105(1):
317 - 323.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. M. Dring, F. E. Davies, J. A. L. Fenton, P. L. Roddam, K. Scott, D. Gonzalez, S. Rollinson, A. C. Rawstron, K. S. Rees-Unwin, C. Li, et al.
A Global Expression-based Analysis of the Consequences of the t(4;14) Translocation in Myeloma
Clin. Cancer Res.,
September 1, 2004;
10(17):
5692 - 5701.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. A. Maxwell, E. Rasmussen, F. Zhan, J. J. Keats, S. Adamia, E. Strachan, M. Crainie, R. Walker, A. R. Belch, L. M. Pilarski, et al.
RHAMM expression and isoform balance predict aggressive disease and poor survival in multiple myeloma
Blood,
August 15, 2004;
104(4):
1151 - 1158.
[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]
|
|
|
|
|
|
|
F. Magrangeas, M.-L. Cormier, G. Descamps, N. Gouy, L. Lode, M.-P. Mellerin, J.-L. Harousseau, R. Bataille, S. Minvielle, and H. Avet-Loiseau
Light-chain only multiple myeloma is due to the absence of functional (productive) rearrangement of the IgH gene at the DNA level
Blood,
May 15, 2004;
103(10):
3869 - 3875.
[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]
|
|
|
|
|
|
|
S. Soverini, M. Cavo, C. Cellini, C. Terragna, E. Zamagni, D. Ruggeri, N. Testoni, P. Tosi, A. de Vivo, M. Amabile, et al.
Cyclin D1 overexpression is a favorable prognostic variable for newly diagnosed multiple myeloma patients treated with high-dose chemotherapy and single or double autologous transplantation
Blood,
September 1, 2003;
102(5):
1588 - 1594.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Robillard, H. Avet-Loiseau, R. Garand, P. Moreau, D. Pineau, M.-J. Rapp, J.-L. Harousseau, and R. Bataille
CD20 is associated with a small mature plasma cell morphology and t(11;14) in multiple myeloma
Blood,
August 1, 2003;
102(3):
1070 - 1071.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Fonseca, E. Blood, M. Rue, D. Harrington, M. M. Oken, R. A. Kyle, G. W. Dewald, B. Van Ness, S. A. Van Wier, K. J. Henderson, et al.
Clinical and biologic implications of recurrent genomic aberrations in myeloma
Blood,
June 1, 2003;
101(11):
4569 - 4575.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Quintanilla-Martinez, M. Kremer, K. Specht, J. Calzada-Wack, M. Nathrath, R. Schaich, H. Hofler, and F. Fend
Analysis of Signal Transducer and Activator of Transcription 3 (Stat 3) Pathway in Multiple Myeloma: Stat 3 Activation and Cyclin D1 Dysregulation Are Mutually Exclusive Events
Am. J. Pathol.,
May 1, 2003;
162(5):
1449 - 1461.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Asosingh, H. De Raeve, I. Van Riet, B. Van Camp, and K. Vanderkerken
Multiple myeloma tumor progression in the 5T2MM murine model is a multistage and dynamic process of differentiation, proliferation, invasion, and apoptosis
Blood,
April 15, 2003;
101(8):
3136 - 3141.
[Abstract]
[Full Text]
[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]
|
|
|
|
|
|
|
G. R. Boersma-Vreugdenhil, T. Peeters, and B. J. E. G. Bast
Translocation of the IgH locus is nearly ubiquitous in multiple myeloma as detected by immuno-FISH
Blood,
February 15, 2003;
101(4):
1653 - 1653.
[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]
|
|
|
|
|
|
|
H. Avet-Loiseau, R. Garand, L. Lode, J.-L. Harousseau, and R. Bataille
Translocation t(11;14)(q13;q32) is the hallmark of IgM, IgE, and nonsecretory multiple myeloma variants
Blood,
February 15, 2003;
101(4):
1570 - 1571.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. L. Bergsagel
Prognostic Factors in Multiple Myeloma: It's in the Genes
Clin. Cancer Res.,
February 1, 2003;
9(2):
533 - 534.
[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]
|
|
|
|
|
|
|
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]
|
|
|
|
|
