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Multiple myeloma with IGH-involving del(14q): report of 34 cases

Multiple myeloma with IGH-involving del(14q): report of 34 cases
Multiple myeloma with IGH-involving del(14q): report of 34 cases
Chromosomal translocations involving the IGH locus on 14q32 are a hallmark of B-cell malignancies. These translocations are particularly frequent in non-hyperdiploid (NHD) multiple myeloma (MM), representing approximately 50% of myeloma cases. MM-associated primary t(14q32) target at least 7 partner genes including cyclins D (CCND1, –D3), MAF transcription factors (CMAF, MAF B and A) and MMSET/FGFR3. Some of the translocations are predictive of clinical outcome. Recently, we identified a novel interstitial del(14q) involving IGH and recurrent in chronic lymphocytic leukaemia and MM (Pospisilova et al, Leukemia, 2007). In spite of extensive studies, the mechanism(s) and molecular consequences of del(14q) remain unknown. We report here 34 cases of plasma cell (PC) malignancies with del(14q) involving IGH, as proven by FISH. Cases were collected in UK and Belgium. The estimated incidence of these aberrations in PC malignancies was 1.4%. There were 13 female and 21 male patients ranging in age from 49 to 86 years (average 68). Twenty seven patients had MM, one had SMM and 6 had MGUS. In almost all cases, the del(14q) was detected at diagnosis. Clinical data of the reported cases have been collected. The del(14q) were roughly mapped by FISH and grouped into 3 categories according to the proximal breakpoint:
del(14)(q24.1q32.33) involving the ZFP36L1 region (11 cases);
deletions proximal to ZFP36L1 (14 cases) and
deletions distal to ZFP36L1 (7 cases).
The size of del(14q) was not determined in 2 cases. Biallelic deletion of TRAF3/14q32.33 recurrently occurring in MM, was detected by FISH in 1 out of 9 analyzed cases. Additional FISH analysis showed that the del(14q) was predominantly associated with NHD tumors (62% vs 38% with hyperdiploid karyotypes) and frequently (60%) accompanied by del(13q), regarded as a poor prognostic factor. All reported cases were negative for t(4;14) and t(11;14); they also showed a normal status of CCND3, CMAF, MAFB and CMYC, when examined. A gain of 1q/CKS1B was found in 57% (8/14) of analyzed cases. The expression pattern of cyclin D1–D3 has been examined.
0006-4971
p.301A
Wlodarska, Iwona
43a4d401-64a8-476a-8ff9-416363712f2e
Ross, Fiona M.
ec0958f8-b992-4e4a-b7e3-c474600390ba
Russell, Lisa J.
cd43806b-dc23-4a75-a263-eb7a4ab90f92
Pospisilova, Helena
2a5a7913-58d0-4eb4-a0b3-8eb9558e561a
Chiecchio, Laura
3d2f63e3-3df1-4655-8478-00ecd89d009c
Van Caillie, Marie-Astrid
66d66057-ac85-4d23-912b-3046d0cbfd09
Dagrada, GianPaolo
a149df7d-0de2-487d-8697-0a8913b998cd
De Wolf-Peeters, Christiane
3b2bbd7f-ff3f-4224-9a55-d8f68e3a81af
Harrison, Christine J.
52da7673-509c-4b88-b92e-0c021c9c7d3e
De Paepe, Pascale
0264ce1e-53f1-4a83-9b3c-8081cf048604
Vandenberghe, Peter
f722b2a9-0680-4d27-9342-a16de8467c69
Michaux, Lucienne
40729cf4-3457-480b-a30d-1b08f686d92d
Wlodarska, Iwona
43a4d401-64a8-476a-8ff9-416363712f2e
Ross, Fiona M.
ec0958f8-b992-4e4a-b7e3-c474600390ba
Russell, Lisa J.
cd43806b-dc23-4a75-a263-eb7a4ab90f92
Pospisilova, Helena
2a5a7913-58d0-4eb4-a0b3-8eb9558e561a
Chiecchio, Laura
3d2f63e3-3df1-4655-8478-00ecd89d009c
Van Caillie, Marie-Astrid
66d66057-ac85-4d23-912b-3046d0cbfd09
Dagrada, GianPaolo
a149df7d-0de2-487d-8697-0a8913b998cd
De Wolf-Peeters, Christiane
3b2bbd7f-ff3f-4224-9a55-d8f68e3a81af
Harrison, Christine J.
52da7673-509c-4b88-b92e-0c021c9c7d3e
De Paepe, Pascale
0264ce1e-53f1-4a83-9b3c-8081cf048604
Vandenberghe, Peter
f722b2a9-0680-4d27-9342-a16de8467c69
Michaux, Lucienne
40729cf4-3457-480b-a30d-1b08f686d92d

Wlodarska, Iwona, Ross, Fiona M., Russell, Lisa J., Pospisilova, Helena, Chiecchio, Laura, Van Caillie, Marie-Astrid, Dagrada, GianPaolo, De Wolf-Peeters, Christiane, Harrison, Christine J., De Paepe, Pascale, Vandenberghe, Peter and Michaux, Lucienne (2007) Multiple myeloma with IGH-involving del(14q): report of 34 cases. Blood, 110 (11), p.301A.

Record type: Article

Abstract

Chromosomal translocations involving the IGH locus on 14q32 are a hallmark of B-cell malignancies. These translocations are particularly frequent in non-hyperdiploid (NHD) multiple myeloma (MM), representing approximately 50% of myeloma cases. MM-associated primary t(14q32) target at least 7 partner genes including cyclins D (CCND1, –D3), MAF transcription factors (CMAF, MAF B and A) and MMSET/FGFR3. Some of the translocations are predictive of clinical outcome. Recently, we identified a novel interstitial del(14q) involving IGH and recurrent in chronic lymphocytic leukaemia and MM (Pospisilova et al, Leukemia, 2007). In spite of extensive studies, the mechanism(s) and molecular consequences of del(14q) remain unknown. We report here 34 cases of plasma cell (PC) malignancies with del(14q) involving IGH, as proven by FISH. Cases were collected in UK and Belgium. The estimated incidence of these aberrations in PC malignancies was 1.4%. There were 13 female and 21 male patients ranging in age from 49 to 86 years (average 68). Twenty seven patients had MM, one had SMM and 6 had MGUS. In almost all cases, the del(14q) was detected at diagnosis. Clinical data of the reported cases have been collected. The del(14q) were roughly mapped by FISH and grouped into 3 categories according to the proximal breakpoint:
del(14)(q24.1q32.33) involving the ZFP36L1 region (11 cases);
deletions proximal to ZFP36L1 (14 cases) and
deletions distal to ZFP36L1 (7 cases).
The size of del(14q) was not determined in 2 cases. Biallelic deletion of TRAF3/14q32.33 recurrently occurring in MM, was detected by FISH in 1 out of 9 analyzed cases. Additional FISH analysis showed that the del(14q) was predominantly associated with NHD tumors (62% vs 38% with hyperdiploid karyotypes) and frequently (60%) accompanied by del(13q), regarded as a poor prognostic factor. All reported cases were negative for t(4;14) and t(11;14); they also showed a normal status of CCND3, CMAF, MAFB and CMYC, when examined. A gain of 1q/CKS1B was found in 57% (8/14) of analyzed cases. The expression pattern of cyclin D1–D3 has been examined.

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More information

Published date: 16 November 2007
Additional Information: ASH Annual Meeting Abstracts, Poster Session: Chromosomal Rearrangements. Abstract 991.

Identifiers

Local EPrints ID: 60775
URI: http://eprints.soton.ac.uk/id/eprint/60775
ISSN: 0006-4971
PURE UUID: 727c43cb-4577-43f8-9fa9-30702086463b

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Date deposited: 11 Nov 2008
Last modified: 11 Dec 2021 18:03

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Contributors

Author: Iwona Wlodarska
Author: Fiona M. Ross
Author: Lisa J. Russell
Author: Helena Pospisilova
Author: Laura Chiecchio
Author: Marie-Astrid Van Caillie
Author: GianPaolo Dagrada
Author: Christiane De Wolf-Peeters
Author: Christine J. Harrison
Author: Pascale De Paepe
Author: Peter Vandenberghe
Author: Lucienne Michaux

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