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Prepublished online as a Blood First Edition Paper on January 16, 2003; DOI 10.1182/blood-2002-09-2825. This Article Full Text (PDF) All Versions of this Article: 2002-09-2825v1 101/10/4137    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Zojer, N. Articles by Sahota, S. S Search for Related Content PubMed PubMed Citation Articles by Zojer, N. Articles by Sahota, S. S Social Bookmarking                   What's this? Submitted September 19, 2002 Accepted December 23, 2002 Patterns of somatic mutations in VH genes reveal pathways of clonal transformation from MGUS to multiple myeloma Niklas Zojer, Heinz Ludwig, Michael Fiegl, Freda K Stevenson, and Surinder S Sahota* Molecular Immunology Group, Tenovus Laboratory, Cancer Sciences Division, Southampton University Hospitals, Southampton, United Kingdom 1st Department of Internal Medicine and Medical Oncology, Wilhelminenspital, Vienna, Austria Division of Hematology and Oncology, Department of Internal Medicine, University Hospital Innsbruck, Innsbruck, Austria * Corresponding author; email: sss1{at}soton.ac.uk. Monoclonal gammopathy of undetermined significance (MGUS) can transform to multiple myeloma (MM). In myeloma, mutated VH genes with sequence homogeneity reveal a post-follicular origin. Previously, some MGUS cases showed mutated VH genes with intraclonal variation, indicating an earlier stage of arrest. We investigated progression from 2/2 MGUS to MM, where VH genes confirmed clonal evolution. In one MGUS case, intraclonal heterogeneity was evident, and transformation to myeloma occurred rapidly with apparent homogeneity in the emergent clone. However, residual MGUS-derived sequences were detectable at this time. Heterogeneity in MGUS does not associate with benign disease, but it indicates an origin from a tumorigenic cell, most likely sIg+ve, undergoing somatic mutation. The remaining case displayed intraclonal homogeneity at the MGUS stage, conceivably resulting from a self-cloning outgrowth from MGUS with heterogeneity. Transformation can occur at either MGUS stage but it involves a single cell in which somatic mutation is then silent. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. M. Tancred, A. R. Belch, T. Reiman, L. M. Pilarski, and J. Kirshner Altered Expression of Fibronectin and Collagens I and IV in Multiple Myeloma and Monoclonal Gammopathy of Undetermined Significance J. Histochem. Cytochem., March 1, 2009; 57(3): 239 - 247. [Abstract] [Full Text] [PDF] D. Gonzalez, M. van der Burg, R. Garcia-Sanz, J. A. Fenton, A. W. Langerak, M. Gonzalez, J. J. M. van Dongen, J. F. San Miguel, and G. J. Morgan Immunoglobulin gene rearrangements and the pathogenesis of multiple myeloma Blood, November 1, 2007; 110(9): 3112 - 3121. [Abstract] [Full Text] [PDF] W. M. Kuehl and P. L. Bergsagel Early Genetic Events Provide the Basis for a Clinical Classification of Multiple Myeloma Hematology, January 1, 2005; 2005(1): 346 - 352. [Abstract] [Full Text] [PDF]

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