The University of Southampton
University of Southampton Institutional Repository

Gene mapping and expression analysis of 16q loss of heterozygosity identifies WWOX and CYLD as being important in determining clinical outcome in multiple myeloma

Gene mapping and expression analysis of 16q loss of heterozygosity identifies WWOX and CYLD as being important in determining clinical outcome in multiple myeloma
Gene mapping and expression analysis of 16q loss of heterozygosity identifies WWOX and CYLD as being important in determining clinical outcome in multiple myeloma
We performed FISH for 16q23 abnormalities in 861 patients with newly diagnosed multiple myeloma and identified del(16q) in 19.5%. In 467 cases in which demographic and survival data were available, del(16q) was associated with a worse overall survival. It was an independent prognostic marker and conferred additional adverse survival impact in cases with the known poor risk cytogenetic factors t(4;14) and del(17p). Gene expression profiling and gene mapping using 500K SNP mapping arrays revealed loss of heterozygosity (LOH) involving 3 regions, the whole of 16q, a region centered on 16q12, the location of CYLD, and a region centered on 16q23, the location of WWOX. CYLD is a negative regulator of the NF-kappaB pathway and cases with low expression of CYLD were used to define a "low-CYLD signature". Cases with 16q LOH or t(14;16) had significantly reduced WWOX expression. WWOX, the site of the translocation breakpoint in t(14;16) cases, is a known tumor suppressor gene involved in apoptosis and we were able to generate a "low-WWOX signature" defined by WWOX expression. These two genes and their corresponding signatures provide an important insight in to the potential mechanisms by which 16q LOH confers poor prognosis.
0006-4971
3291-3300
Jenner, Matthew W.
af4d9ce0-1282-4eb3-8440-98b16ee7cc85
Leone, Paola E.
e510164f-5de4-4c77-bca7-769d52a51953
Walker, Brian A.
7e45e107-ca85-4368-8673-7177f2328405
Ross, Fiona M.
ec0958f8-b992-4e4a-b7e3-c474600390ba
Johnson, David C.
95bd8f42-2b59-4788-86dd-a32087bf554b
Gonzalez, David
23765c4d-1658-40fd-a487-bc11bad2aea3
Chiecchio, Laura
3d2f63e3-3df1-4655-8478-00ecd89d009c
Dachs Cabanas, Elisabet
6369a501-9cba-4f33-b3c4-347c226acf5c
Dagrada, Gian Paolo
a6e0f6d8-2aa8-4cda-a595-7d75bc5cacf8
Nightingale, Mathew
d6fa28d9-e479-4d12-bce9-8981aa86b37a
Protheroe, Rebecca K.M.
b2c9973f-ccf1-44a4-8e37-e76ee7e8ec0b
Stockley, David
fd8e48fa-cd20-4326-8608-795fb84cfda4
Else, Monica
3d354259-1969-4d47-9eea-5b95daaf2089
Dickens, Nicholas J.
a22b3b23-76ab-493a-b34e-669a2c3ee1c4
Cross, Nicholas C.P.
f87650da-b908-4a34-b31b-d62c5f186fe4
Davies, Faith E.
9ea9e143-ac51-431b-8cb5-57b8dc0a38af
Morgan, Gareth J.
d285dcf8-ac2c-4fe0-acf9-4787eb025939
Jenner, Matthew W.
af4d9ce0-1282-4eb3-8440-98b16ee7cc85
Leone, Paola E.
e510164f-5de4-4c77-bca7-769d52a51953
Walker, Brian A.
7e45e107-ca85-4368-8673-7177f2328405
Ross, Fiona M.
ec0958f8-b992-4e4a-b7e3-c474600390ba
Johnson, David C.
95bd8f42-2b59-4788-86dd-a32087bf554b
Gonzalez, David
23765c4d-1658-40fd-a487-bc11bad2aea3
Chiecchio, Laura
3d2f63e3-3df1-4655-8478-00ecd89d009c
Dachs Cabanas, Elisabet
6369a501-9cba-4f33-b3c4-347c226acf5c
Dagrada, Gian Paolo
a6e0f6d8-2aa8-4cda-a595-7d75bc5cacf8
Nightingale, Mathew
d6fa28d9-e479-4d12-bce9-8981aa86b37a
Protheroe, Rebecca K.M.
b2c9973f-ccf1-44a4-8e37-e76ee7e8ec0b
Stockley, David
fd8e48fa-cd20-4326-8608-795fb84cfda4
Else, Monica
3d354259-1969-4d47-9eea-5b95daaf2089
Dickens, Nicholas J.
a22b3b23-76ab-493a-b34e-669a2c3ee1c4
Cross, Nicholas C.P.
f87650da-b908-4a34-b31b-d62c5f186fe4
Davies, Faith E.
9ea9e143-ac51-431b-8cb5-57b8dc0a38af
Morgan, Gareth J.
d285dcf8-ac2c-4fe0-acf9-4787eb025939

Jenner, Matthew W., Leone, Paola E., Walker, Brian A., Ross, Fiona M., Johnson, David C., Gonzalez, David, Chiecchio, Laura, Dachs Cabanas, Elisabet, Dagrada, Gian Paolo, Nightingale, Mathew, Protheroe, Rebecca K.M., Stockley, David, Else, Monica, Dickens, Nicholas J., Cross, Nicholas C.P., Davies, Faith E. and Morgan, Gareth J. (2007) Gene mapping and expression analysis of 16q loss of heterozygosity identifies WWOX and CYLD as being important in determining clinical outcome in multiple myeloma. Blood, 110 (9), 3291-3300. (doi:10.1182/blood-2007-02-075069).

Record type: Article

Abstract

We performed FISH for 16q23 abnormalities in 861 patients with newly diagnosed multiple myeloma and identified del(16q) in 19.5%. In 467 cases in which demographic and survival data were available, del(16q) was associated with a worse overall survival. It was an independent prognostic marker and conferred additional adverse survival impact in cases with the known poor risk cytogenetic factors t(4;14) and del(17p). Gene expression profiling and gene mapping using 500K SNP mapping arrays revealed loss of heterozygosity (LOH) involving 3 regions, the whole of 16q, a region centered on 16q12, the location of CYLD, and a region centered on 16q23, the location of WWOX. CYLD is a negative regulator of the NF-kappaB pathway and cases with low expression of CYLD were used to define a "low-CYLD signature". Cases with 16q LOH or t(14;16) had significantly reduced WWOX expression. WWOX, the site of the translocation breakpoint in t(14;16) cases, is a known tumor suppressor gene involved in apoptosis and we were able to generate a "low-WWOX signature" defined by WWOX expression. These two genes and their corresponding signatures provide an important insight in to the potential mechanisms by which 16q LOH confers poor prognosis.

Text
blood-2007-02-075069v1.pdf - Version of Record
Restricted to Repository staff only
Request a copy

More information

Submitted date: 26 February 2007
Published date: 3 July 2007

Identifiers

Local EPrints ID: 47933
URI: http://eprints.soton.ac.uk/id/eprint/47933
ISSN: 0006-4971
PURE UUID: 34456305-a084-4e69-a0b2-c5a7d4c12fe8
ORCID for Nicholas C.P. Cross: ORCID iD orcid.org/0000-0001-5481-2555

Catalogue record

Date deposited: 10 Aug 2007
Last modified: 16 Mar 2024 03:23

Export record

Altmetrics

Contributors

Author: Matthew W. Jenner
Author: Paola E. Leone
Author: Brian A. Walker
Author: Fiona M. Ross
Author: David C. Johnson
Author: David Gonzalez
Author: Laura Chiecchio
Author: Elisabet Dachs Cabanas
Author: Gian Paolo Dagrada
Author: Mathew Nightingale
Author: Rebecca K.M. Protheroe
Author: David Stockley
Author: Monica Else
Author: Nicholas J. Dickens
Author: Faith E. Davies
Author: Gareth J. Morgan

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 http://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.

×