High incidence of cryptic translocations involving the Ig heavy chain gene in multiple myeloma, as shown by fluorescence in situ hybridization

Abstract Chromosome rearrangement of 14q32.33 has recurrently occurred with variable partner sites, including 11q13.3, 8q24.1, 18q21.3, and 6p21.1 in multiple myeloma (MM). To assess the actual incidence of 14q32.33 translocation and to elucidate its implication in the pathogenesis of MM, we studied 42 patients with MM, plasma cell leukemia, or plasmacytoma and 5 with monoclonal gammopathy with undetermined significance (MGUS) by G-banding and molecular cytogenetic methods. Using double-color fluorescence in situ hybridization (DCFISH) with 2 Ig heavy chain (IgH) gene probes, a yeast artificial chromosome (YAC) clone containing variable region, and a phage clone containing γ constant region, 14q32.33 translocation was detected as split signals of the IgH gene in 31 patients with plasma cell malignancies and 3 with MGUS. In contrast, of 40 patients who were assessed by G-banding, 3 (7.5%) showed the 14q+ chromosome. DCFISH detected a split of the IgH gene on interphase nuclei in 34 (73.9%) of 46 patients analyzed, whereas on metaphase spreads, it was in 22 (51.2%) of 43 patients analyzed. Interphase DCFISH was particularly useful to detect 14q32.33 translocation in 17 (65.4%) of 26 patients with normal karyotypes. Donor sites were identified in 11 of 22 patients demonstrated as carrying 14q32.33 translocation by metaphase FISH. Chromosome t(11; 14)(q13.3; q32.33) was detected in 5 patients, t(8; 14)(q24.1; q32.33) in 2, t(14; 18)(q32.33; q21.3) in 2, and t(7; 14)(q32.1; q32.33) in 1. A complex 14q32.33 translocation involving 3q and 16q24 was detected in 1 patient. Myeloma cells with t(7; 14) showed myelomonocytoid surface antigen. Because rearrangements of 14q32.33 were closely associated with translocation of proto-oncogenes into the IgH gene, our findings indicate that 14q32.33 translocation with various partner chromosomes is a critical event in the pathogenesis of MM and MGUS.

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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 ◽

10.1182/blood.v90.2.526.526_526_534 ◽

1997 ◽

Vol 90 (2) ◽

pp. 526-534 ◽

Cited By ~ 5

Author(s):

Kazuhiro Nishida ◽

Akiko Tamura ◽

Naozo Nakazawa ◽

Yutaka Ueda ◽

Tatsuo Abe ◽

...

Keyword(s):

Multiple Myeloma ◽

In Situ Hybridization ◽

Plasma Cell ◽

Heavy Chain ◽

Plasma Cell Leukemia ◽

Critical Event ◽

Chain Gene ◽

Cell Leukemia ◽

Ig Heavy Chain

Chromosome rearrangement of 14q32.33 has recurrently occurred with variable partner sites, including 11q13.3, 8q24.1, 18q21.3, and 6p21.1 in multiple myeloma (MM). To assess the actual incidence of 14q32.33 translocation and to elucidate its implication in the pathogenesis of MM, we studied 42 patients with MM, plasma cell leukemia, or plasmacytoma and 5 with monoclonal gammopathy with undetermined significance (MGUS) by G-banding and molecular cytogenetic methods. Using double-color fluorescence in situ hybridization (DCFISH) with 2 Ig heavy chain (IgH) gene probes, a yeast artificial chromosome (YAC) clone containing variable region, and a phage clone containing γ constant region, 14q32.33 translocation was detected as split signals of the IgH gene in 31 patients with plasma cell malignancies and 3 with MGUS. In contrast, of 40 patients who were assessed by G-banding, 3 (7.5%) showed the 14q+ chromosome. DCFISH detected a split of the IgH gene on interphase nuclei in 34 (73.9%) of 46 patients analyzed, whereas on metaphase spreads, it was in 22 (51.2%) of 43 patients analyzed. Interphase DCFISH was particularly useful to detect 14q32.33 translocation in 17 (65.4%) of 26 patients with normal karyotypes. Donor sites were identified in 11 of 22 patients demonstrated as carrying 14q32.33 translocation by metaphase FISH. Chromosome t(11; 14)(q13.3; q32.33) was detected in 5 patients, t(8; 14)(q24.1; q32.33) in 2, t(14; 18)(q32.33; q21.3) in 2, and t(7; 14)(q32.1; q32.33) in 1. A complex 14q32.33 translocation involving 3q and 16q24 was detected in 1 patient. Myeloma cells with t(7; 14) showed myelomonocytoid surface antigen. Because rearrangements of 14q32.33 were closely associated with translocation of proto-oncogenes into the IgH gene, our findings indicate that 14q32.33 translocation with various partner chromosomes is a critical event in the pathogenesis of MM and MGUS.

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Comparison of the Rate of Detection of Immunoglobulin Heavy Chain Gene Rearrangement by Fluoresecence In Situ Hybridization Probes in Multiple Myeloma

Annals of Laboratory Medicine ◽

10.3343/kjlm.2006.26.5.317 ◽

2006 ◽

Vol 26 (5) ◽

pp. 317-322

Author(s):

Hye Yoon Chung ◽

Cha Ja See ◽

Jung Eun Choi ◽

Hyun Jung Min ◽

Han Ik Cho ◽

...

Keyword(s):

Multiple Myeloma ◽

In Situ Hybridization ◽

Heavy Chain ◽

Gene Rearrangement ◽

Chain Gene ◽

Heavy Chain Gene ◽

Immunoglobulin Heavy Chain Gene ◽

Hybridization Probes ◽

Chain Gene Rearrangement

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Assignment1 of the human dynein heavy chain gene DNAH17L to human chromosome 17p12 by in situ hybridization and radiation hybrid mapping

Cytogenetic and Genome Research ◽

10.1159/000015254 ◽

1999 ◽

Vol 84 (3-4) ◽

pp. 188-189 ◽

Cited By ~ 4

Author(s):

L. Bartoloni ◽

J.-L.C. Blouin ◽

A.J. Sainsbury ◽

A. Gos ◽

M.A. Morris ◽

...

Keyword(s):

In Situ Hybridization ◽

Human Chromosome ◽

Heavy Chain ◽

Radiation Hybrid ◽

Radiation Hybrid Mapping ◽

Chain Gene ◽

Hybrid Mapping ◽

Heavy Chain Gene ◽

Dynein Heavy Chain

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Immunoglobulin heavy-chain gene rearrangement in B-cell non-Hodgkin lymphoma using the fluorescence in-situ hybridization technique

The Egyptian Journal of Haematology ◽

10.4103/1110-1067.161295 ◽

2015 ◽

Vol 40 (2) ◽

pp. 90

Author(s):

GhadaM ElGohary ◽

MohamedA. M. Mekawy ◽

ManalM Ismail ◽

MahiraI El Mogy ◽

AhmedM. M. Mostafa ◽

...

Keyword(s):

In Situ Hybridization ◽

Heavy Chain ◽

Gene Rearrangement ◽

Chain Gene ◽

Hybridization Technique ◽

Heavy Chain Gene ◽

Immunoglobulin Heavy Chain Gene ◽

Non Hodgkin Lymphoma ◽

Chain Gene Rearrangement

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Translocation t(11;14)(q13;q32) is the hallmark of IgM, IgE, and nonsecretory multiple myeloma variants

Blood ◽

10.1182/blood-2002-08-2436 ◽

2003 ◽

Vol 101 (4) ◽

pp. 1570-1571 ◽

Cited By ~ 101

Author(s):

Hervé Avet-Loiseau ◽

Richard Garand ◽

Laurence Lodé ◽

Jean-Luc Harousseau ◽

Régis Bataille

Keyword(s):

Multiple Myeloma ◽

In Situ Hybridization ◽

Fluorescence In Situ Hybridization ◽

Fold Increase ◽

Major Interest ◽

High Incidence ◽

Very High

In an attempt to address the issue of cytogenetic features of multiple myeloma (MM) variants, we have analyzed a series of 8 IgM, 9 IgD, 2 IgE, and 14 nonsecretory (NS) MM cases using fluorescence in situ hybridization. A very high incidence (83%) of t(11;14)(q13;q32) was detected in the IgM (7 of 8), IgE (2 of 2), and NS (11 of 14) MM cases, but not in the IgD cases (2 of 9). Of note, no t(4;14) was observed in this cohort of patients. This increased incidence of t(11;14) was associated with 2 dominant features in these variants, namely, a “lymphoplasmacytic” presentation mainly in IgM MM and a lower secreting capacity in the others, 2 features previously associated with t(11;14). Of major interest, t(11;14) was never observed in Waldenström macroglobulinemia or in IgG/IgA “lymphoplasmacytic” lymphomas. Thus, for unknown reasons, t(11;14) is the hallmark of IgM, IgE, and NS MM, (but not IgD MM), with a 5-fold increase of its incidence compared to that of IgG and IgA MM.

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