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Blood, 1 March 2007, Vol. 109, No. 5, pp. 2089-2099. Prepublished online as a Blood First Edition Paper on October 31, 2006; DOI 10.1182/blood-2006-04-018770. This Article Full Text (PDF) All Versions of this Article: blood-2006-04-018770v1 109/5/2089    most recent Alert me when this article is cited Alert me if a correction is posted 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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Cheng, S. H. Articles by Ng, H. K. Search for Related Content PubMed PubMed Citation Articles by Cheng, S. H. Articles by Ng, H. K. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 26, 2006 Accepted October 19, 2006 4q loss is potentially an important genetic event in MM tumorigenesis: identification of a tumor suppressor gene regulated by promoter methylation at 4q13.3, platelet factor 4 Suk Hang Cheng, Margaret HL Ng*, Kin Mang Lau, Herman SY Liu, Joyce CW Chan, Angela BY Hui, Kwok Wai Lo, Hua Jiang, Jian Hou, Raymond W Chu, Wai Shan Wong, Natalie PH Chan, and Ho Keung Ng The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Pamela Youde Nethersole Eastern Hospital, Hong Kong Chang Zheng Hospital, Second Military Medical University, China * Corresponding author; email: margaretng{at}cuhk.edu.hk. In this study, we have elucidated the chromosomal imbalances in the multistep pathogenesis and delineated several critical tumor suppressor gene (TSG) loci in multiple myeloma (MM). By using comparative genomic hybridization, allelotyping and multicolor interphase fluorescence in-situ hybridization, 5 MM cell lines and bone marrow CD138+ plasma cells from 88 Chinese patients with monoclonal gammopathy of undetermined significance (MGUS), early and advanced stages of MM were investigated. In all MGUS and MM samples, chromosome copy number abnormalities were detected. Higher number of chromosomal imbalances and specific genetic alterations are involved in MGUS to MM transition (-6q, +3p and +1p) and MM progression (+2p and +9q). In addition to -13q, we first found high frequencies (42-46%) of -4q involving high percentages (70-74%) of clonal plasma cells in both MGUS and MM, suggesting that inactivation of TSG in this region is also a potentially critical genetic event in MM tumorigenesis. By high resolution allelotyping, we defined a common deletion region on 4q13.3 and found that a candidate TSG platelet factor 4 was frequently silenced by promoter hypermethylation in MM (15/28) and MM cell lines (5/5). These data have opened up a new approach in the molecular targeting therapy and provide novel insights into MM tumorigenesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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