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Timing of acquisition of deletion 13 in plasma cell dyscrasias is dependent on genetic context

Timing of acquisition of deletion 13 in plasma cell dyscrasias is dependent on genetic context
Timing of acquisition of deletion 13 in plasma cell dyscrasias is dependent on genetic context
Background: multiple myeloma, monoclonal gammopathy of undetermined significance and smoldering multiple myeloma harbor common chromosomal abnormalities but the prevalence and relative association of aberrations in these diagnostic groups remains controversial. We investigated these aspects in a large series of patients.
Design and Methods: chromosome 13 deletion ({Delta}13), deletion of TP53, ploidy status and immunoglobulin heavy chain (IgH) translocations were evaluated by fluorescence in situ hybridization in patients with monoclonal gammopathy of undetermined significance (n=189), smoldering multiple myeloma (n=127) and multiple myeloma (n=400).
Results: overall, {Delta}13 (25%, 34% and 47%), 16q23 deletions (6%, 8% and 21%) and 17p13 deletions (3%, 1% and 10%) were less frequent in patients with monoclonal gammopathy of undetermined significance and smoldering multiple myeloma than in those with multiple myeloma. When distinct genetic groups were considered, no differences in the prevalence of {Delta}13 were found with t(4;14)(p16;q32) and t(14;16)(q32;q23) among the three diagnostic groups; in contrast {Delta}13 was rarer in t(11;14)(q13;q32) in patients with monoclonal gammopathy (1/28) and smoldering myeloma (2/13) than in those with multiple myeloma (40%). Similar results were seen for the few t(6;14)(p21;q32) cases: 0/3 patients with monoclonal gammopathy or smoldering myeloma had the {Delta}13, whereas 4/6 (67%) patients with multiple myeloma and this translocation also had the deletion. In multiple myeloma patients with both an IgH translocation and {Delta}13, the proportions of cells affected by the two abnormalities were similar, as was the case for t(4;14) and t(14;16) monoclonal gammopathy patients positive for {Delta}13. In contrast, in monoclonal gammopathy patients with t(14;20)(q32;q11), the translocation was present in almost all cells, while the {Delta}13 was present in only a sub-population.
Conclusions: these results indicate that the presence and time of occurrence of {Delta}13 depends on the presence of specific concurrent abnormalities. The observation that {Delta}13 was extremely rare in monoclonal gammopathy of undetermined significance and smoldering multiple myeloma with translocations directly involving cyclin D genes (CCND1 and CCND3) suggest a possible role of {Delta}13 in the progression of the disease specifically in these genetic sub-groups. (clinicaltrials.gov identifier: ISRCTN 68454111; UKCRN ID 1176)
deletion 13, plasma cell dyscrasias, genetic context
0390-6078
1708-1713
Chiecchio, Laura
3d2f63e3-3df1-4655-8478-00ecd89d009c
Dagrada, Gian Paolo
a6e0f6d8-2aa8-4cda-a595-7d75bc5cacf8
Ibrahim, Aahraf H.
f4a9ca35-ded1-4770-a16c-52cc6d7f538c
Dachs Cabanas, Elizabet
be59568a-d373-4785-8d6c-41383e11590b
Protheroe, Rebbeca K.M.
b2c9973f-ccf1-44a4-8e37-e76ee7e8ec0b
Stockley, David M.
fd8e48fa-cd20-4326-8608-795fb84cfda4
Orchard, Kim H.
794654ab-d6cc-488a-ac11-c9217433c7a2
Cross, Nicholas C.P.
f87650da-b908-4a34-b31b-d62c5f186fe4
Harrison, Christine J.
52da7673-509c-4b88-b92e-0c021c9c7d3e
Ross, Fiona M.
ec0958f8-b992-4e4a-b7e3-c474600390ba
on behalf of the UK Myeloma Forum
Chiecchio, Laura
3d2f63e3-3df1-4655-8478-00ecd89d009c
Dagrada, Gian Paolo
a6e0f6d8-2aa8-4cda-a595-7d75bc5cacf8
Ibrahim, Aahraf H.
f4a9ca35-ded1-4770-a16c-52cc6d7f538c
Dachs Cabanas, Elizabet
be59568a-d373-4785-8d6c-41383e11590b
Protheroe, Rebbeca K.M.
b2c9973f-ccf1-44a4-8e37-e76ee7e8ec0b
Stockley, David M.
fd8e48fa-cd20-4326-8608-795fb84cfda4
Orchard, Kim H.
794654ab-d6cc-488a-ac11-c9217433c7a2
Cross, Nicholas C.P.
f87650da-b908-4a34-b31b-d62c5f186fe4
Harrison, Christine J.
52da7673-509c-4b88-b92e-0c021c9c7d3e
Ross, Fiona M.
ec0958f8-b992-4e4a-b7e3-c474600390ba

Chiecchio, Laura, Dagrada, Gian Paolo, Ibrahim, Aahraf H., Dachs Cabanas, Elizabet, Protheroe, Rebbeca K.M., Stockley, David M., Orchard, Kim H., Cross, Nicholas C.P., Harrison, Christine J. and Ross, Fiona M. , on behalf of the UK Myeloma Forum (2009) Timing of acquisition of deletion 13 in plasma cell dyscrasias is dependent on genetic context. Haematologica, 94 (12), 1708-1713. (doi:10.3324/haematol.2009.011064).

Record type: Article

Abstract

Background: multiple myeloma, monoclonal gammopathy of undetermined significance and smoldering multiple myeloma harbor common chromosomal abnormalities but the prevalence and relative association of aberrations in these diagnostic groups remains controversial. We investigated these aspects in a large series of patients.
Design and Methods: chromosome 13 deletion ({Delta}13), deletion of TP53, ploidy status and immunoglobulin heavy chain (IgH) translocations were evaluated by fluorescence in situ hybridization in patients with monoclonal gammopathy of undetermined significance (n=189), smoldering multiple myeloma (n=127) and multiple myeloma (n=400).
Results: overall, {Delta}13 (25%, 34% and 47%), 16q23 deletions (6%, 8% and 21%) and 17p13 deletions (3%, 1% and 10%) were less frequent in patients with monoclonal gammopathy of undetermined significance and smoldering multiple myeloma than in those with multiple myeloma. When distinct genetic groups were considered, no differences in the prevalence of {Delta}13 were found with t(4;14)(p16;q32) and t(14;16)(q32;q23) among the three diagnostic groups; in contrast {Delta}13 was rarer in t(11;14)(q13;q32) in patients with monoclonal gammopathy (1/28) and smoldering myeloma (2/13) than in those with multiple myeloma (40%). Similar results were seen for the few t(6;14)(p21;q32) cases: 0/3 patients with monoclonal gammopathy or smoldering myeloma had the {Delta}13, whereas 4/6 (67%) patients with multiple myeloma and this translocation also had the deletion. In multiple myeloma patients with both an IgH translocation and {Delta}13, the proportions of cells affected by the two abnormalities were similar, as was the case for t(4;14) and t(14;16) monoclonal gammopathy patients positive for {Delta}13. In contrast, in monoclonal gammopathy patients with t(14;20)(q32;q11), the translocation was present in almost all cells, while the {Delta}13 was present in only a sub-population.
Conclusions: these results indicate that the presence and time of occurrence of {Delta}13 depends on the presence of specific concurrent abnormalities. The observation that {Delta}13 was extremely rare in monoclonal gammopathy of undetermined significance and smoldering multiple myeloma with translocations directly involving cyclin D genes (CCND1 and CCND3) suggest a possible role of {Delta}13 in the progression of the disease specifically in these genetic sub-groups. (clinicaltrials.gov identifier: ISRCTN 68454111; UKCRN ID 1176)

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More information

Published date: December 2009
Keywords: deletion 13, plasma cell dyscrasias, genetic context

Identifiers

Local EPrints ID: 69942
URI: https://eprints.soton.ac.uk/id/eprint/69942
ISSN: 0390-6078
PURE UUID: b209b021-ab9e-4006-b6d1-007a650e03c6
ORCID for Kim H. Orchard: ORCID iD orcid.org/0000-0003-2276-3925
ORCID for Nicholas C.P. Cross: ORCID iD orcid.org/0000-0001-5481-2555

Catalogue record

Date deposited: 11 Dec 2009
Last modified: 24 Sep 2019 00:49

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