Multiple myeloma shows no intra-disease clustering of immunoglobulin heavy chain genes.
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.


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.
Division of Hematology, Department of Experimental Medicine and Oncology, University of Turin, Italy.
Simone
S
Ferrero
Daniela
D
Capello
Mirija
M
Svaldi
Michela
M
Boi
Daniela
D
Gatti
Daniela
D
Drandi
Davide
D
Rossi
Sara
S
Barbiero
Barbara
B
Mantoan
Elisabetta
E
Mantella
Manuela
M
Zanni
Paola
P
Ghione
Alessandra
A
Larocca
Roberto
R
Passera
Francesco
F
Bertoni
Valter
V
Gattei
Francesco
F
Forconi
Luca
L
Laurenti
Giovanni
G
Del Poeta
Roberto
R
Marasca
Sergio
S
Cortelazzo
Gianluca
G
Gaidano
Antonio
A
Palumbo
Mario
M
Boccadoro
Marco
M
Ladetto
D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D022801:Complementarity Determining Regions / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D057225:Data Mining; D030561:Databases, Nucleic Acid; D050438:Genes, Immunoglobulin Heavy Chain / Q000276:immunology*; D006801:Humans; D005810:Multigene Family / Q000276:immunology; D009101:Multiple Myeloma / Q000235:genetics* / Q000276:immunology; D009194:Myeloma Proteins / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D017422:Sequence Analysis, DNA; D027041:Somatic Hypermutation, Immunoglobulin / Q000276:immunology
D022801:Complementarity Determining Regions; D009194:Myeloma Proteins; C017551:myeloma immunoglobulins