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Blood, 1 February 2007, Vol. 109, No. 3, pp. 1228-1232. Prepublished online as a Blood First Edition Paper on July 13, 2006; DOI 10.1182/blood-2006-05-024661. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-05-024661v1 109/3/1228    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 Gonzalez-Paz, N. Articles by Fonseca, R. Search for Related Content PubMed PubMed Citation Articles by Gonzalez-Paz, N. Articles by Fonseca, R. Related Collections Neoplasia Oncogenes and Tumor Suppressors Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Tumor suppressor p16 methylation in multiple myeloma: biological and clinical implications Natalia Gonzalez-Paz1, Wee J. Chng2, Rebecca F. McClure3, Emily Blood4, Martin M. Oken4, Brian Van Ness4, C. David James5, Paul J. Kurtin3, Kimberly Henderson1, Gregory J. Ahmann2, Morie Gertz1, Martha Lacy1, Angela Dispenzieri1, Philip R. Greipp1, and Rafael Fonseca2 1 Department of Hematology, Mayo Clinic College of Medicine, Rochester, MN; 2 Department of Hematology-Oncology, Mayo Clinic, Scottsdale, AZ; 3 Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, MN; 4 Eastern Cooperative Oncology Group (ECOG); and 5 Department of Experimental Pathology, Mayo Clinic College of Medicine, Rochester, MN The biological and clinical implications of p16 gene methylation in multiple myeloma (MM) are still unclear despite previous studies. In this comprehensive study, using methylation-specific PCR (MS-PCR), we show that p16 methylation is relatively common and occurs in monoclonal gammopathy of undetermined significance (MGUS; n = 17), smoldering multiple myeloma (SMM; n = 40), and MM (n = 522) at a prevalence of 24%, 28%, and 34%, respectively. However, p16 methylation does not appear to affect gene expression level. In a large cohort of patients with long-term follow-up information (n = 439), there was no difference in overall survival between patients with or without p16 methylation. We also found no association between p16 methylation and the main cytogenetic categories, although it was more common among patients with 17p13.1 deletions (p53 locus), a genetic progression event in MM. In addition, p16 methylation has no apparent effect on the cycle because there was also no difference in the plasma cell labeling index (a direct measurement of proliferation) between patients with and without p16 methylation. Our results question a major role for p16 methylation in the oncogenesis of the PC neoplasm, and we now believe p16 methylation may be a marker for overall epigenetic changes associated with disease progression, with no obvious direct biological or clinical consequences. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: V. Bollati, S. Fabris, V. Pegoraro, D. Ronchetti, L. Mosca, G. L. Deliliers, V. Motta, P. A. Bertazzi, A. Baccarelli, and A. Neri Differential repetitive DNA methylation in multiple myeloma molecular subgroups Carcinogenesis, August 1, 2009; 30(8): 1330 - 1335. [Abstract] [Full Text] [PDF] M. A. Dawson, S. S. Opat, Y. Taouk, M. Donovan, M. Zammit, K. Monaghan, N. Horvath, A. W. Roberts, H. M. Prince, M. Hertzberg, et al. Clinical and Immunohistochemical Features Associated with a Response to Bortezomib in Patients with Multiple Myeloma Clin. Cancer Res., January 15, 2009; 15(2): 714 - 722. [Abstract] [Full Text] [PDF] A. Dispenzieri, R. A. Kyle, J. A. Katzmann, T. M. Therneau, D. Larson, J. Benson, R. J. Clark, L. J. Melton III, M. A. Gertz, S. K. Kumar, et al. Immunoglobulin free light chain ratio is an independent risk factor for progression of smoldering (asymptomatic) multiple myeloma Blood, January 15, 2008; 111(2): 785 - 789. [Abstract] [Full Text] [PDF] A. Dib, B. Barlogie, J. D. Shaughnessy Jr, and W. M. Kuehl Methylation and expression of the p16INK4A tumor suppressor gene in multiple myeloma Blood, February 1, 2007; 109(3): 1337 - 1338. [Full Text] [PDF]

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