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.