Top

Published in:

01-04-2008 | Original Article

Close relation between 14q32/IGH translocations and chromosome 13 abnormalities in multiple myeloma: a high incidence of 11q13/CCND1 and 16q23/MAF

Authors: Madoka Takimoto, Kohei Ogawa, Yo Kato, Tasuku Saito, Takao Suzuki, Michiko Irei, Yasushi Shibuya, Yoshinori Suzuki, Masayuki Kato, Yasuyuki Inoue, Masatomo Takahashi, Hiroki Sugimori, Ikuo Miura

Published in: International Journal of Hematology | Issue 3/2008

Abstract

Many B-cell tumors have chromosomal translocations that result from failures of the immunoglobulin (Ig) gene during V(D)J recombination, somatic hypermutation (SHM), and class switch recombination (CSR). Nearly half of all multiple myeloma (MM) patients have 14q32/IGH translocations in CSR, including the five common translocations of 11q13/CCND1, 6p21/CCND3, 4p16/FGFR3, 16q23/MAF, and 20q11/MAFB. Although 14q32/IGH translocations are closely related to the biological features of MM, the most consistent and powerful prognostic factor has been reported to be the loss of all (monosomy 13/−13) or part of chromosome 13 (del(13)(q14)/13q−). Our fluorescence in situ hybridization (FISH) analysis method was designed to detect −13/13q− and 14q32/IGH rearrangements in 23 MM patients. FISH disclosed 14q32/IGH translocations in 10 of the 23 (43.5%) patients. The common translocation partners of 14q32/IGH were 11q13/CCND1 (five patients) and 16q23/MAF (four patients), followed in third place by 4p16/FGFR3 (one patient). Nine of the ten patients carrying 14q32/IGH translocations had −13/13q−. Abnormalities of chromosome 13 included −13 in seven (70%) and del(13)(q14) in two (20%). Our results suggest a significant correlation between the presence of 14q32/IGH translocations and chromosome 13 abnormalities (P = 0.0276) in MM patients.

Kuehl WM, Bergsagel PL. Multiple myeloma: evolving genetic events and host interactions. Nat Rev Cancer. 2002;2:175–87.PubMedCrossRef

Hideshima T, Bergsagel PL, Kuehl WM, Anderson KC. Advances in biology of multiple myeloma: clinical applications. Blood. 2004;104:607–18.PubMedCrossRef

Myeloma Trialists’ Collaborative Group. Combination chemotherapy versus melphalan plus prednisone as treatment for multiple myeloma an overview of 6,633 patients from 27 randomized trials. J Clin Oncol 1998; 16:3832–42.

Attal M, Harousseau JL, Facon T, Guilhot F, Doyen C, Fuzibet JG, et al. Single versus double autologous stem-cell transplantation for multiple myeloma. N Engl J Med. 2003;349:2495–502.PubMedCrossRef

Garban F, Attal M, Michallet M, Hulin C, Bourhis JH, Yakoub-Agha I, et al. Prospective comparison of autologous stem cell transplantation followed by dose-reduced allograft (IFM99–03 trial) with tandem autologous stem cell transplantation (IFM99-04 trial) in high-risk de novo multiple myeloma. Blood. 2006;107:3474–80.PubMedCrossRef

Bruno B, Rotta M, Patriarca F, Mordini N, Allione B, Carnevale-Schianca F, et al. A comparison of allografting with autografting for newly diagnosed myeloma. N Engl J Med. 2007;356:1110–20.PubMedCrossRef

Avet-Loiseau H, Attal M, Moreau P, Charbonnel C, Garban F, Hulin C, et al. Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myélome. Blood. 2007;109:3489–95.PubMedCrossRef

Greipp PR, Miguel JS, Durie BGM, Crowley JJ, Barlogie B, Bladé J, et al. International staging system for multiple myeloma. J Clin Oncol. 2005;23:3412–20.PubMedCrossRef

Durie BGM, Harousseau JL, Miguel JS, Bladé J, Barlogie B, Anderson K, et al. International uniform response criteria for multiple myeloma. Leukemia. 2006;20:1467–73.PubMedCrossRef

10.

Facon T, Avet-Loiseau H, Guillerm G, Moreau P, Geneviève F, Zandecki M, et al. Chromosome 13 abnormalities identified by FISH analysis and serum β₂-microglobulin produce a powerful myeloma staging system for patients receiving high-dose therapy. Blood. 2001;97:1566–71.PubMedCrossRef

11.

Nishida K, Tamura A, Nakazawa N, Ueda Y, Abe T, Matsuda F, et al. The Ig heavy chain gene is frequently involved in chromosomal translocations in multiple myeloma and plasma cell leukemia as detected by in situ hybridization. Blood. 1997;90:526–34.PubMed

12.

Durie BGM. Staging and kinetics of multiple myeloma. Semin Oncol. 1986;13:300–9.PubMed

13.

Nimura T, Miura I, Kobayashi Y, Yoshioka T, Kume M, Takahashi N, et al. Cytogenetic study of 48 patients with multiple myeloma and related disorders. J Clin Exp Hematop. 2003;43:53–60.CrossRef

14.

ISCN. An International System for Human Cytogenetic Nomenclature, Shaffer LG, Tommerup N editors. Basel: S. Karger; 2005. pp. 1–120.

15.

Calasanz MJ, Cigudosa JC, Odero MD, Ferreira C, Ardanaz MT, Fraile A, et al. Cytogenetic analysis of 280 patients with multiple myeloma and related disorders: primary breakpoints and clinical correlations. Genes Chromosomes Cancer. 1997;18:84–93.PubMedCrossRef

16.

Harrison CJ, Mazzullo H, Cheung KL, Gerrard G, Jalali GR, Mehta A, et al. Cytogenetics of multiple myeloma: interpretation of fluorescence in situ hybridization results. Br J Haematol. 2003;120:944–52.PubMedCrossRef

17.

Gutiérrez NC, García JL, Hernández JM, Lumbreras E, Castellanos M, Rasillo A, et al. Prognostic and biologic significance of chromosomal imbalances assessed by comparative genomic hybridization in multiple myeloma. Blood. 2004;104:2661–6.PubMedCrossRef

18.

Dewald GW, Therneau T, Larson D, Lee YK, Smoley S, Paternoster S, et al. Relationship of patient survival and chromosome anomalies detected in metaphase and/or interphase cells at diagnosis of myeloma. Blood. 2005;106:3553–8.PubMedCrossRef

19.

Chesi M, Bergsagel PL, Brents LA, Smith CM, Gerhard DS, Kuehl WM. Dysregulation of cyclin D1 by translocation into an IgH gamma switch region in two multiple myeloma cell lines. Blood. 1996;88:674–81.PubMed

20.

Chesi M, Bergsagel PL, Shonukan OO, Martelli ML, Brents LA, Chen T, et al. Frequent dysregulation of the c-maf proto-oncogene at 16q23 by translocation to an Ig locus in multiple myeloma. Blood. 1998;91:4457–63.PubMed

21.

Chesi M, Nardini E, Lim RSC, Smith KD, Kuehl WM, Bergsagel PL. The t(4;14) Translocation in Myeloma Dysregulates Both FGFR3 and a Novel Gene, MMSET, Resulting in IgH/MMSET Hybrid Transcripts. Blood. 1998;92:3025–34.PubMed

22.

Fonseca R, Barlogie B, Bataille R, Bastard C, Bergsagel PL, Chesi M, et al. Genetics and Cytogenetics of Multiple Myeloma. Cancer Res. 2004;64:1546–58.PubMedCrossRef

23.

Bergsagel PL, Kuehl WM. Molecular pathogenesis and a consequent classification of multiple myeloma. J Clin Oncol. 2005;23:6333–8.PubMedCrossRef

24.

Iida S, Ueda R. Multistep tumorigenesis of multiple myeloma: Its molecular delineation. Int J Hematol. 2003;77:207–12.PubMedCrossRef

25.

Fonseca R, Blood EA, Oken MM, Kyle RA, Dewald GW, Bailey RJ, et al. Myeloma and the t(11;14)(q13;q32); evidence for a biologically defined unique subset of patients. Blood. 2002;99:3735–41.PubMedCrossRef

26.

Garand R, Avet-Loiseau H, Accard F, Moreau P, Harousseau JL, Bataille R. t(11;14) and t(4;14) translocations correlated with mature lymphoplasmacytoid and immature morphology, respectively, in multiple myeloma. Leukemia. 2003;17:2032–5.PubMedCrossRef

27.

Chesi M, Nardini E, Brents LA, Schröck E, Ried T, Kuehl WM, et al. Frequent translocation t(4;14)(p16.3;q32.3) in multiple myeloma is associated with increased expression and activating mutations of fibroblast growth factor receptor 3. Nat Genet. 1997;16:260–4.PubMedCrossRef

28.

Moreau P, Facon T, Leleu X, Morineau N, Huyghe P, Harousseau JL, et al. Recurrent 14q32 translocations determine the prognosis of multiple myeloma, especially in patients receiving intensive chemotherapy. Blood. 2002;100:1579–83.PubMedCrossRef

29.

Nakazawa N, Nishida K, Tamura A, Kobayashi M, Iwai T, Horiike S, et al. Interphase detection of t(4;14)(p16.3;q32.3) by in situ hybridization and FGFR3 overexpression in plasma cell malignancies. Cancer Genet Cytogenet. 2000;117:89–96.PubMedCrossRef

30.

Alexander DD, Mink PJ, Adami HO, Cole P, Mandel JS, Oken MM, et al. Multiple myeloma: a review of the epidemiologic literature. Int J Cancer. 2007;120:40–61.PubMedCrossRef

31.

Lymphoma Study Group of Japanese Pathologists. The world health organization classification of malignant lymphomas in Japan: incidence of recently recognized entities. Pathol Int. 2000;50:696–702.

32.

Shaughnessy J Jr, Tian E, Sawyer J, Bumm K, Landes R, Badros A, et al. High incidence of chromosome 13 deletion in multiple myeloma detected by multiprobe interphase FISH. Blood. 2000;96:1505–11.PubMed

33.

Chiecchio L, Protheroe RKM, Ibrahim AH, Cheung KL, Rudduck C, Dagrada GP, et al. Deletion of chromosome 13 detected by conventional cytogenetics is a critical prognostic factor in myeloma. Leukemia. 2006;20:1610–7.PubMedCrossRef

34.

Fonseca R, Oken MM, Harrington D, Bailey RJ, Van Wier SA, Henderson KJ, et al. Deletions of chromosome 13 in multiple myeloma identified by interphase FISH usually denote large deletions of the q arm or monosomy. Leukemia. 2001;15:981–6.PubMedCrossRef

35.

Döhner H, Stilgenbauer S, Benner A, Leupolt E, Kröber A, Bullinger L, et al. Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med. 2000;343:1910–6.PubMedCrossRef

36.

Dicker F, Schnittger S, Haferlach T, Kern W, Schoch C. Immunostimulatory oligonucleotide-induced metaphase cytogenetics detects chromosomal aberrations in 80% of CLL patients: a study of 132 CLL cases with correlation to FISH, IgV_H status and CD38 expression. Blood. 2006;108:3152–60.PubMedCrossRef

Title: Close relation between 14q32/IGH translocations and chromosome 13 abnormalities in multiple myeloma: a high incidence of 11q13/CCND1 and 16q23/MAF
Authors: Madoka Takimoto
Kohei Ogawa
Yo Kato
Tasuku Saito
Takao Suzuki
Michiko Irei
Yasushi Shibuya
Yoshinori Suzuki
Masayuki Kato
Yasuyuki Inoue
Masatomo Takahashi
Hiroki Sugimori
Ikuo Miura
Publication date: 01-04-2008
Publisher: Springer Japan
Published in: International Journal of Hematology / Issue 3/2008
Print ISSN: 0925-5710
Electronic ISSN: 1865-3774
DOI: https://doi.org/10.1007/s12185-008-0039-x

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2008

A case of adult Langerhans cell histiocytosis showing successfully regenerated osseous tissue of the skull after chemotherapy

Effect of mesenchymal stem cell transplantation on the engraftment of human hematopoietic stem cells and leukemic cells in mice model

A case of factor X (FX) deficiency due to novel mutation V196M, FX Hofu

Clinical features of late cytomegalovirus infection after hematopoietic stem cell transplantation

Implications of sphingosine kinase 1 expression level for the cellular sphingolipid rheostat: relevance as a marker for daunorubicin sensitivity of leukemia cells

Identification of genes potentially involved in supporting hematopoietic stem cell activity of stromal cell line MC3T3-G2/PA6

Keynote webinar | Spotlight on antibody–drug conjugates in cancer