1. Multiple myeloma shows no intra-disease clustering of immunoglobulin heavy chain genes.
- Author
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Ferrero S, Capello D, Svaldi M, Boi M, Gatti D, Drandi D, Rossi D, Barbiero S, Mantoan B, Mantella E, Zanni M, Ghione P, Larocca A, Passera R, Bertoni F, Gattei V, Forconi F, Laurenti L, Del Poeta G, Marasca R, Cortelazzo S, Gaidano G, Palumbo A, Boccadoro M, and Ladetto M
- Subjects
- B-Lymphocytes immunology, B-Lymphocytes pathology, Complementarity Determining Regions chemistry, Complementarity Determining Regions immunology, Data Mining, Databases, Nucleic Acid, Humans, Multigene Family immunology, Multiple Myeloma immunology, Myeloma Proteins chemistry, Myeloma Proteins immunology, Sequence Analysis, DNA, Somatic Hypermutation, Immunoglobulin immunology, Complementarity Determining Regions genetics, Genes, Immunoglobulin Heavy Chain immunology, Multiple Myeloma genetics, Myeloma Proteins genetics
- Abstract
Background: Characterization of the immunoglobulin gene repertoire has improved our understanding of the immunopathogenesis of lymphoid tumors. Early B-lymphocyte precursors of multiple myeloma are known to exist and might be susceptible to antigenic drive., Design and Methods: To verify this hypothesis, we collected a database of 345 fully readable multiple myeloma immunoglobulin sequences. We characterized the immunoglobulin repertoire, analyzed the somatic hypermutation load, and investigated for stereotyped receptor clusters., Results: Compared to the normal immunoglobulin repertoire, multiple myeloma displayed only modest differences involving only a few genes, showing that the myeloma immunoglobulin repertoire is the least skewed among mature B-cell tumors. Median somatic hypermutation load was 7.8%; median length of complementarity determining-region 3 was 15.5 amino acids. Clustering analysis showed the absence of myeloma specific clusters and no similarity with published chronic lymphocytic leukemia or lymphoma subsets., Conclusions: Analysis of multiple myeloma immunoglobulin repertoire does not support a pathogenetic role for antigen selection in this tumor.
- Published
- 2012
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