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Blood, 1 November 2007, Vol. 110, No. 9, pp. 3291-3300. Prepublished online as a Blood First Edition Paper on July 3, 2007; DOI 10.1182/blood-2007-02-075069. This Article Full Text Full Text (PDF) Supplemental Tables All Versions of this Article: blood-2007-02-075069v1 110/9/3291    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Jenner, M. W. Articles by Morgan, G. J. Search for Related Content PubMed PubMed Citation Articles by Jenner, M. W. Articles by Morgan, G. J. Related Collections Clinical Trials and Observations Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Gene mapping and expression analysis of 16q loss of heterozygosity identifies WWOX and CYLD as being important in determining clinical outcome in multiple myeloma Matthew W. Jenner1, Paola E. Leone1, Brian A. Walker1, Fiona M. Ross2, David C. Johnson1, David Gonzalez1, Laura Chiecchio2, Elisabet Dachs Cabanas2, Gian Paolo Dagrada2, Mathew Nightingale2, Rebecca K. M. Protheroe2, David Stockley2, Monica Else1, Nicholas J. Dickens1, Nicholas C. P. Cross2, Faith E. Davies1, and Gareth J. Morgan1 1 Section of Haemato-Oncology, Institute of Cancer Research, London; 2 Leukaemia Research Fund UK Myeloma Forum Cytogenetics Group, Wessex Regional Genetics Laboratory, Salisbury, United Kingdom 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-B 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. Xu, J. R. Houck, W. Fan, P. Wang, Y. Chen, M. Upton, N. D. Futran, S. M. Schwartz, L. P. Zhao, C. Chen, et al. Simultaneous Isolation of DNA and RNA from the Same Cell Population Obtained by Laser Capture Microdissection for Genome and Transcriptome Profiling J. Mol. Diagn., March 1, 2008; 10(2): 129 - 134. [Abstract] [Full Text] [PDF]

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