The University of Southampton
University of Southampton Institutional Repository

Deletion of 16q identified by FISH is an independent adverse prognostic marker in multiple myeloma

Deletion of 16q identified by FISH is an independent adverse prognostic marker in multiple myeloma
Deletion of 16q identified by FISH is an independent adverse prognostic marker in multiple myeloma
Deletion of 16q (del(16q)) has been identified in 15% of newly diagnosed myeloma but the prognostic impact has not been determined. We performed FISH on CD138 selected plasma cells from 861 newly diagnosed patients with multiple myeloma from the LRF UK Myeloma Forum Cytogenetics Database. Del(16q) occurred in 168/861 cases (19.5%) and was significantly associated with deletion 13q (54.8% vs 43.5%, P50.009), deletion of IgH (19.6% vs 8.7%, Po0.001), deletion 17p (20.7% vs 7.2%, Po0.001) and nonhyperdiploid status (47.9% vs 40.3%, P50.043). Clinical and survival data was available in 505 patients. Median age was 65 years (range 33–92) and median follow-up was 19 months. Del(16q) showed no association with baseline clinical and demographic parameters but was associated with a significantly worse overall survival (median survival 36 months vs not reached, P50.025). Moreover, del(16q) conferred additional adverse impact in combination with the known poor risk cytogenetic factors t(4;14) and deletion 17p (del(17p)). Median survival for del(16q) and t(4;14) was 13 months, del (16q) alone 36 months, t(4;14) alone not reached, P50.001. Median survival for del(16q) and del(17p) was 17 months, del(16q) alone 36 months, del(17p) alone not reached, P50.003. Multivariate analysis confirmed that del(16q) retained independence as an adverse prognostic marker (P50.003) along with t(4;14), t(14;16), light chain isotype, WHO performance status, ISS and age.
Integration of gene mapping with global gene expression data in a subset of 55 cases identified two potential tumour suppressor genes located on 16q, CYLD and WWOX. We have shown that loss of CYLD dysregulates the NFkB pathway and loss of WWOX dysregulates apoptosis via p73, both of crucial importance in myeloma biology. WWOX is also a common fragile site gene and deletions at other common fragile sites were identified that may also contribute to myeloma pathogenesis. An update of this mapping and expression data including the NFkB signature associated with 16q deletion will be presented.
time, multiple myeloma, england, publishing
0007-1048
p.1
Jenner, M.W.
ce6104bc-9713-483a-9224-f29fd3c9cef1
Leone, P.E.
045ed52d-e481-4b4c-bfc7-4df5420e53f0
Walker, B.A.
d808cee3-7459-4d1a-af1a-be12674488a8
Johnson, D.C.
a9c9c920-b5ef-4ae9-b68d-30c87ec7f21a
Chiecchio, L.
48f9d8f0-c80c-4486-af21-2cd4a27810bc
Cabanas, E.D.
0c77bdcf-1330-4710-a0b4-bc88b883a1e8
Dagrada, G.P.
5af7a8c6-2db5-4d7c-8936-e21ada0bfc28
Nightingale, M.
15a695b5-b0e8-4288-acf4-313b250a33c0
Protheroe, R.K.M.
b2c9973f-ccf1-44a4-8e37-e76ee7e8ec0b
Stockley, D.
fd8e48fa-cd20-4326-8608-795fb84cfda4
Else, M.
70d3fa26-c25f-4753-a696-d5820208e767
Dickens, N.J.
6d23d227-305e-4a83-8944-44efc8e32cf6
Ross, F.M.
ec0958f8-b992-4e4a-b7e3-c474600390ba
Cross, N.C.P.
f87650da-b908-4a34-b31b-d62c5f186fe4
Davies, F.E.
3db5c54e-9852-4caf-91d9-8b339f68a632
Morgan, G.J.
7e5206cc-8a58-410c-9ea5-9022b1532ace
Jenner, M.W.
ce6104bc-9713-483a-9224-f29fd3c9cef1
Leone, P.E.
045ed52d-e481-4b4c-bfc7-4df5420e53f0
Walker, B.A.
d808cee3-7459-4d1a-af1a-be12674488a8
Johnson, D.C.
a9c9c920-b5ef-4ae9-b68d-30c87ec7f21a
Chiecchio, L.
48f9d8f0-c80c-4486-af21-2cd4a27810bc
Cabanas, E.D.
0c77bdcf-1330-4710-a0b4-bc88b883a1e8
Dagrada, G.P.
5af7a8c6-2db5-4d7c-8936-e21ada0bfc28
Nightingale, M.
15a695b5-b0e8-4288-acf4-313b250a33c0
Protheroe, R.K.M.
b2c9973f-ccf1-44a4-8e37-e76ee7e8ec0b
Stockley, D.
fd8e48fa-cd20-4326-8608-795fb84cfda4
Else, M.
70d3fa26-c25f-4753-a696-d5820208e767
Dickens, N.J.
6d23d227-305e-4a83-8944-44efc8e32cf6
Ross, F.M.
ec0958f8-b992-4e4a-b7e3-c474600390ba
Cross, N.C.P.
f87650da-b908-4a34-b31b-d62c5f186fe4
Davies, F.E.
3db5c54e-9852-4caf-91d9-8b339f68a632
Morgan, G.J.
7e5206cc-8a58-410c-9ea5-9022b1532ace

Jenner, M.W., Leone, P.E., Walker, B.A., Johnson, D.C., Chiecchio, L., Cabanas, E.D., Dagrada, G.P., Nightingale, M., Protheroe, R.K.M., Stockley, D., Else, M., Dickens, N.J., Ross, F.M., Cross, N.C.P., Davies, F.E. and Morgan, G.J. (2007) Deletion of 16q identified by FISH is an independent adverse prognostic marker in multiple myeloma. British Journal of Haematology, 137 (Supp/1), p.1. (doi:10.1111/j.1365-2141.2007.06557.x).

Record type: Article

Abstract

Deletion of 16q (del(16q)) has been identified in 15% of newly diagnosed myeloma but the prognostic impact has not been determined. We performed FISH on CD138 selected plasma cells from 861 newly diagnosed patients with multiple myeloma from the LRF UK Myeloma Forum Cytogenetics Database. Del(16q) occurred in 168/861 cases (19.5%) and was significantly associated with deletion 13q (54.8% vs 43.5%, P50.009), deletion of IgH (19.6% vs 8.7%, Po0.001), deletion 17p (20.7% vs 7.2%, Po0.001) and nonhyperdiploid status (47.9% vs 40.3%, P50.043). Clinical and survival data was available in 505 patients. Median age was 65 years (range 33–92) and median follow-up was 19 months. Del(16q) showed no association with baseline clinical and demographic parameters but was associated with a significantly worse overall survival (median survival 36 months vs not reached, P50.025). Moreover, del(16q) conferred additional adverse impact in combination with the known poor risk cytogenetic factors t(4;14) and deletion 17p (del(17p)). Median survival for del(16q) and t(4;14) was 13 months, del (16q) alone 36 months, t(4;14) alone not reached, P50.001. Median survival for del(16q) and del(17p) was 17 months, del(16q) alone 36 months, del(17p) alone not reached, P50.003. Multivariate analysis confirmed that del(16q) retained independence as an adverse prognostic marker (P50.003) along with t(4;14), t(14;16), light chain isotype, WHO performance status, ISS and age.
Integration of gene mapping with global gene expression data in a subset of 55 cases identified two potential tumour suppressor genes located on 16q, CYLD and WWOX. We have shown that loss of CYLD dysregulates the NFkB pathway and loss of WWOX dysregulates apoptosis via p73, both of crucial importance in myeloma biology. WWOX is also a common fragile site gene and deletions at other common fragile sites were identified that may also contribute to myeloma pathogenesis. An update of this mapping and expression data including the NFkB signature associated with 16q deletion will be presented.

Full text not available from this repository.

More information

Published date: 17 April 2007
Keywords: time, multiple myeloma, england, publishing

Identifiers

Local EPrints ID: 59878
URI: https://eprints.soton.ac.uk/id/eprint/59878
ISSN: 0007-1048
PURE UUID: 38ba1c08-b303-406a-9d69-eb2bdcb65e9f
ORCID for N.C.P. Cross: ORCID iD orcid.org/0000-0001-5481-2555

Catalogue record

Date deposited: 05 Sep 2008
Last modified: 06 Jun 2018 12:49

Export record

Altmetrics

Contributors

Author: M.W. Jenner
Author: P.E. Leone
Author: B.A. Walker
Author: D.C. Johnson
Author: L. Chiecchio
Author: E.D. Cabanas
Author: G.P. Dagrada
Author: M. Nightingale
Author: R.K.M. Protheroe
Author: D. Stockley
Author: M. Else
Author: N.J. Dickens
Author: F.M. Ross
Author: N.C.P. Cross ORCID iD
Author: F.E. Davies
Author: G.J. Morgan

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of https://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×