Deletion of 16q identified by FISH is an independent adverse prognostic marker in multiple myeloma
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).
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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.
|Keywords:||time, multiple myeloma,england, publishing|
Q Science > QR Microbiology
|Divisions:||University Structure - Pre August 2011 > School of Health Sciences
University Structure - Pre August 2011 > School of Medicine
University Structure - Pre August 2011 > School of Medicine > Human Genetics
|Date Deposited:||05 Sep 2008|
|Last Modified:||01 Jun 2011 02:45|
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