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Blood, 1 January 2005, Vol. 105, No. 1, pp. 317-323. Prepublished online as a Blood First Edition Paper on August 31, 2004; DOI 10.1182/blood-2004-03-0833. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-03-0833v1 105/1/317    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 Rasmussen, T. Articles by Dahl, I. M. S. Search for Related Content PubMed PubMed Citation Articles by Rasmussen, T. Articles by Dahl, I. M. S. Related Collections Neoplasia Cell Cycle Oncogenes and Tumor Suppressors Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Possible roles for activating RAS mutations in the MGUS to MM transition and in the intramedullary to extramedullary transition in some plasma cell tumors Thomas Rasmussen, Michael Kuehl, Marianne Lodahl, Hans E. Johnsen, and Inger Marie S. Dahl From the Department of Hematology L 54P4, Herlev Hospital, University of Copenhagen, Herlev, Denmark; Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda Naval Hospital, Bethesda, MD; and Section of Hematology, University Hospital, Tromsø, Norway. To assess a possible role in tumor progression, the occurrence and type of K- and N-RAS mutations were determined in purified tumor cells, including samples from patients with premalignant monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma (MM), and extramedullary plasma cell (PC) tumors (ExPCTs). Immunophenotypic aberrant PCs were flow sorted from 20 MGUS, 58 MM, and 13 ExPCT patients. One RAS mutation was identified in 20 MGUS tumors (5%), in contrast to a much higher prevalence of RAS mutations in all stages of MM (about 31%). Further, oncogene analyses showed that RAS mutations are not evenly distributed among different molecular subclasses of MM, with the prevalence being increased in MM-expressing cyclin D1 (P = .015) and decreased in MM with t(4;14) (P = .055). We conclude that RAS mutations often provide a genetic marker if not a causal event in the evolution of MGUS to MM. Surprisingly, RAS mutations were absent in bone marrow tumor cells from all patients with ExPCT, a result significantly different from intramedullary MM (P = .001). From 3 of 6 patients with paired intramedullary and extramedullary PCs and identical immunoglobulin heavy chain gene (IgH) sequences, RAS mutations were identified only in extramedullary PCs, suggesting a role for RAS mutations in the transition from intramedullary to extramedullary tumor. (Blood. 2005;105:317-323) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: W. J. Chng, S. A. Van Wier, G. J. Ahmann, J. M. Winkler, S. M. Jalal, P. L. Bergsagel, M. Chesi, M. C. Trendle, M. M. Oken, E. Blood, et al. A validated FISH trisomy index demonstrates the hyperdiploid and nonhyperdiploid dichotomy in MGUS Blood, September 15, 2005; 106(6): 2156 - 2161. [Abstract] [Full Text] [PDF]

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