Jenner, M.W. et al. (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), pp. 3291-3300. (doi: 10.1182/blood-2007-02-075069)
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Abstract
We performed fluorescent in situ hybridization (FISH) for 16q23 abnormalities in 861 patients with newly diagnosed multiple myeloma and identified deletion of 16q [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 (OS). 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 single-nucleotide polymorphism (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 the WW domain-containing oxidoreductase gene 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 2 genes and their corresponding pathways provide an important insight into the potential mechanisms by which 16q LOH confers poor prognosis.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Dickens, Dr Nicholas |
Authors: | Jenner, M.W., Leone, P.E., Walker, B.A., Ross, F.M., Johnson, D.C., Gonzalez, D., Chiecchio, L., Dachs Cabanas, E., Dagrada, G.P., Nightingale, M., Protheroe, R.K.M., Stockley, D., Else, M., Dickens, N.J., Cross, N.C.P., Davies, F.E., and Morgan, G.J. |
College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
Journal Name: | Blood |
Publisher: | American Society of Hematology |
ISSN: | 0006-4971 |
ISSN (Online): | 1528-0020 |
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