Chromosome abnormalities detected in metaphases from multiple myeloma (MM) cells have a clear impact on prognosis and response to therapy. Thirteen out of 50 (26%) patients with plasma cell disorders and abnormal karyotypes (11 with MM and 2 with plasma cell leukemia (PCL)) were selected for inclusion in the present report based on the presence of karyotypes with new and/or infrequent structural aberrations. Thirty-three new rearrangements, including a novel recurrent aberration: psu dic(5;1)(q35;q10), were detected. Chromosome 1 was the most frequently involved. Gains of genetic material (57%) were noted more frequently than losses (43%). Three rearrangements that were observed only once in the literature appear to be recurrent from our data: del(16)(q13), del(5)(p13) and i(3)(q10), the latter being a single structural aberration in the karyotype. Clinical parameters from our series were compared with 2 control groups: 20 MM cases with recurrent aberrations in MM/PCL with a similar distribution of abnormalities associated with poor prognosis (group 1), and 40 with normal karyotypes and fluorescence in situ hybridization analysis (group 2). Significantly increased serum calcium levels (p = 0.022) in patients with new and/or infrequent chromosome changes with respect to both control groups, and a higher percentage of bone marrow plasma cell infiltration (p = 0.005), β2 microglobulin, and lactate dehydrogenase levels (p < 0.0001) compared to group 2 were observed. Our results suggest that some of these novel rearrangements may be capable to deregulate genetic mechanisms related to the development and/or progression of the disease. The finding of new recurrent aberrations supports this hypothesis.

Avet-Loiseau H, Caviet A, Brigaudeau C, Callet-Bauchu E, Terre C, et al: Cytogenetic, interphase, and multicolor fluorescence in situ hybridization analyses in primary plasma cell leukemia: a study of 40 patients at diagnosis, on behalf of the Intergroupe Francophone du Myélome and the Groupe Français de Cytogénétique Hématologique. Blood 97:822–825 (2001).
Avet-Loiseau H, Attal M, Moreau P, Charbonnel C, Garban F, et al: Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myélome. Blood 109:3489–3495 (2007).
Avet-Loiseau H, Li C, Magrangeas F, Gouraud W, Charbonnel C, et al: Prognostic significance of copy-number alterations in multiple myeloma. J Clin Oncol 27:4585–4590 (2009).
Bang SM, Kim YR, Cho HI, Chi HS, Seo EJ, et al: Identification of 13q deletion, trisomy 1q, and IgH rearrangement as the most frequent chromosomal changes found in Korean patients with multiple myeloma. Cancer Genet Cytogenet 168:124–132 (2006).
Beà S, Campo E: Secondary genomic alterations in non-Hodgkin’s lymphomas: tumor-specific profiles with impact on clinical behavior. Haematologica 93:641–645 (2008).
Carrasco DR, Tonon G, Huang Y, Zhang Y, Sinha R, et al: High-resolution genomic profiles define distinct clinico-pathogenetic subgroups of multiple myeloma patients. Cancer Cell 9:313–325 (2006).
Chang H, Qi X, Jiang A, Xu W, Trieu Y, et al: 1p21 deletions are strongly associated with 1q21 gains and are an independent adverse prognostic factor for the outcome of high-dose chemotherapy in patients with multiple myeloma. Bone Marrow Transp 45:117–121 (2010).
Chiecchio L, Protheroe RK, Ibrahim AH, Cheung KL, Rudduck C, et al: Deletion of chromosome 13 detected by conventional cytogenetics is a critical prognostic factor in myeloma. Leukemia 20:1610–1617 (2006).
Chng WJ, Glebov O, Bergsagel PL, Kuehl WM: Genetic events in the pathogenesis of multiple myeloma. Best Pract Res Clin Haematol 20:571–596 (2007).
Chng WJ, Gertz MA, Chung T-H, Van Wier S, Keats JJ, et al: Correlation between array-comparative genomic hybridization-defined genomic gains and losses and survival: identification of 1p31–32 deletion as a prognostic factor in myeloma. Leukemia 24:833–842 (2010).
Cigudosa JC, Rao PH, Calasanz MJ, Odero MD, Michaeli J, et al: Characterization of nonrandom chromosomal gains and losses in multiple myeloma by comparative genomic hybridization. Blood 91:3007–3010 (1998).
Colović M, Janković G, Suvajdzić N, Milić N, Dordević V, et al: Thirty patients with primary plasma cell leukemia: a single center experience. Med Oncol 25:154–160 (2008).
Cuneo A, Balsamo R, Roberti MG, Bardi A, Piva N, et al: Interleukin-3 plus interleukin-6 may improve chromosomal analysis of multiple myeloma: cytologic and cytogenetic evidence in thirty-four patients. Cancer Genet Cytogenet 90:171–175 (1996).
Dewald GM, Kyle RA, Hicks GA, Greipp PR: The clinical significance of cytogenetic studies in 100 patients with multiple myeloma, plasma cell leukemia, or amyloidosis. Blood 66:380–390 (1985).
Dewald GM, Therneau T, Larson D, Lee YK, Fink S, et al: Relationship of patient survival and chromosome anomalies detected in metaphase and/or interphase cell at diagnosis of myeloma. Blood 106:3552–3558 (2005).
Durie BG, Salmon E: A clinical staging system for multiple myeloma: correlation of measured myeloma cell mass with presenting clinical features, response to treatment and survival. Cancer 36:842–854 (1975).
Fassas AB, Tricot G: Chromosome 13 deletion/hypodiploidy and prognosis in multiple myeloma patients. Leuk Lymphoma 45:1083–1091 (2004).
Fonseca R, Oken MM, Harrington D, Bailey RJ, Van Wier SA, et al: Deletions of chromosome 13 in multiple myeloma identified by interphase FISH usually denote large deletions of the q arm or monosomy. Leukemia 15:981–986 (2001).
Fonseca R, Debes-Marun CS, Picken EB, Dewald GW, Bryant SC, et al: The recurrent IgH translocations are highly associated with nonhyperdiploid variant multiple myeloma. Blood 102:2562–2567 (2003).
Fonseca R, Bergsagel PL, Drasch J, Shaughnessy J, Gutierrez N, et al: International Myeloma Working Group molecular classification of multiple myeloma: spotlight review. Leukemia 23:2210–2221 (2009).
Greipp P, San Miguel J, Durie BG, Crowley J, Barlogie B, et al: International staging system for multiple myeloma. J Clin Oncol 23:3412–3420 (2005).
Gutiérrez NC, García JL, Hernández JM, Lumbreras E, Castellanos M, et al: Prognostic and biologic significance of chromosomal imbalances assessed by comparative genomic hybridization in multiple myeloma. Blood 104:2661–2666 (2004).
Hanamura I, Stewart JP, Huang Y, Zhan F, Santra M, et al: Frequent gain of chromosome band 1q21 in plasma-cell dyscrasias detected by fluorescence in situ hybridization: incidence increases from MGUS to relapsed myeloma and is related to prognosis and disease progression following tandem stem-cell transplantation. Blood 108:1724–1732 (2006).
Hideshima T, Mitsiades C, Ikeda H, Chauhan D, Raje N, et al: A proto-oncogen BCL6 is up-regulated in bone marrow microenvironment in multiple myeloma cells. Blood 115:3772–3775 (2010).
Hsi ED, Steinle R, Balasa B, Szmania S, Draksharapu A, et al: CS1, a potential new therapeutic antibody target for the treatment of multiple myeloma. Clin Cancer Res 14:2772–2784 (2008).
Inamoto Y, Kurahashi S, Imahashi N, Fukushima N, Adachi T, et al: Combinations of cytogenetics and international scoring system can predict poor prognosis in multiple myeloma after high-dose chemotherapy and autologous stem cell transplantation. Am J Hematology 84:283–286 (2009).
ISCN: An International System for Human Cytogenetic Nomenclature: Shaffer LG, Slovak ML, Campbell LJ (eds) (Karger, Basel 2009).
Itoyama T, Nanjangud G, Chen W, Dyomin VG, Teruya-Feldstein J, et al: Molecular cytogenetic analysis of genomic instability at the 1q12–22 chromosomal site in B-cell non-Hodgkin lymphoma. Genes Chrom Cancer 35:318–328 (2002).
Jenner MW, Leone PE, Walker BA, Ross FM, Johnson DC, et al: Gene mapping and expression analysis of 16q loss of heterozygosity identifies WWOX and CYLD as being important in determining clinical outcome in multiple myeloma. Blood 110:3291–3300 (2007).
Kyle RA, Rajkumar SV: Multiple myeloma. N Eng J Med 351:1860–1873 (2004).
Largo C, Saéz B, Alvarez S, Suela J, Ferreira B, et al: Multiple myeloma primary cells show a highly rearranged unbalanced genome with amplifications and homozygous deletions irrespective of the presence of immunoglobulin-related chromosome translocations. Haematologica 92:795–802 (2007).
Le Baccon P, Laroux D, Dascalescu C, Duley S, Marais D, et al: Novel evidence of a role for chromosome 1 pericentric heterochromatin in the pathogenesis of B-cell lymphoma and multiple myeloma. Genes Chrom Cancer 32:250–264 (2001).
McKenna RW, Kyle RA, Kuehl WM, Grogan TM, Harris NL, et al: Plasma cell neoplasms. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, et al (eds): WHO Classification of Tumors of Haematopoietic and Lymphoid Tissues, pp 200–213 (IARC Press, Lyon 2008).
Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer: Mitelman F, Johansson B, Mertens F (eds): Available from URL: (2011).
Nilsson T, Lenhoff S, Rylander L, Höglund M, Turesson I, et al: High frequencies of chromosomal aberrations in multiple myeloma and monoclonal gammopathy of undetermined significance in direct chromosome preparation. Br J Haematol 126:487–494 (2004).
Sawyer JR, Tricot G, Mattox S, Jagannath S, Barlogie B: Jumping translocations of chromosome 1q in multiple myeloma: Evidence for a mechanism involving decondensation of pericentromeric heterochromatin. Blood 91:1732–1741 (1998).
Sawyer JR, Tricot G, Lukacs JL, Binz RL, Tian E, et al: Genomic instability in multiple myeloma: evidence for jumping segmental duplications of chromosome arm 1q. Genes Chrom Cancer 42:92–106 (2005).
Sawyer JR, Tian E, Thomas E, Koller M, Stangeby C, et al: Evidence for a novel mechanism for gene amplification in multiple myeloma: 1q12 pericentromeric heterochromatin mediates breakage-fusion-bridge cycles of a 1q12 approximately 23 amplicon. Br J Haematol 147:484–494 (2009).
Sawyer JR: The prognostic significance of cytogenetics and molecular profiling in multiple myeloma. Cancer Genet 204:3–12 (2011).
Seong C, Delasalle K, Hayes K, Weber D, Dimopoulos M, et al: Prognostic value of cytogenetics in multiple myeloma. Br J Haematol 101:189–194 (1998).
Shaughnessy J, Tian E, Sawyer J, Bumm K, Landes R, et al: High incidence of chromosome 13 deletion in multiple myeloma detected by multiprobe interphase FISH. Blood 96:1505–1511 (2000).
Shaughnessy JD Jr, Zhan F, Burington BE, Huang Y, Colla S, et al: A validated gene expression model of high-risk multiple myeloma is defined by deregulated expression of genes mapping to chromosome 1. Blood 109:2276–2284 (2007).
Smadja NV, Bastard C Brigaudeau C, Leroux D, Fruchart C: Hypodiploidy is a major prognostic factor in multiple myeloma. Blood 98:2229–2238 (2001).
Smadja NV, Leroux D, Soulier J, Dumont S, Arnould C, et al: Further cytogenetic characterization of multiple myeloma confirms that 14q32 translocations are a very rare event in hyperdiploid cases. Genes Chrom Cancer 38:234–239 (2003).
Stewart AK, Bergsagel PL, Greipp PR, Dispenzieri A, Gertz MA, et al: A practical guide to defininig high-risk myeloma for clinical trials, patient counseling and choice of therapy. Leukemia 21:529–534 (2007).
Tai Y, Soydan E, Song W, Fulciniti MT, Kim K, et al: CS1 promotes multiple myeloma cell adhesion, clonogenic growth, and tumorigenicity via c-maf-mediated interactions with bone marrow stromal cells. Blood 113:4309–4318 (2009).
Tiedemann RE, Gonzalez-Paz N, Kyle RA, Santana-Davila R, Price-Troska T, et al: Genetic aberrations and survival in plasma cell leukemia. Leukemia 22:1044–1052 (2008).
Walker BA, Leone PE, Jenner MW, Li C, Gonzalez D, et al: Integration of global SNP-based mapping and expression arrays reveals key regions, mechanisms, and genes important in the pathogenesis of multiple myeloma. Blood 108:1733–1743 (2006).
Zhan F, Sawyer J, Tricot G: The role of cytogenetics in myeloma. Leukemia 20:1484–1486 (2006a).
Zhan F, Huang Y, Colla S, Stewart JP, Hanamura I, et al: The molecular classification of multiple myeloma. Blood 108:2020–2028 (2006b).
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.