Molecular characteristics and gene segment usage in IGH gene rearrangements in multiple myeloma.
OBJECTIVE
Analysis of IgH rearrangements in B-cell malignancies has provided clinical researchers with a wide range of information during the last few years. However, only a few studies have contributed to the characterization of these features in multiple myeloma (MM), and they have been focused on the analysis of the expressed IgH allele only. Comparison between the expressed and the non-functional IgH alleles allows further characterizion of the selection processes to which pre-myeloma cells are submitted.


METHODS
We analyzed a cohort of 84 untreated MM patients in order to characterize their functional VDJH and non-functional DJH rearrangements. The pattern of mutations and gene segment usage for both types of rearrangements was analyzed by polymerase chain reaction and sequencing.


RESULTS
VH3 and VH1 family members were over- and under-represented, respectively. VH3-30 and VH3-15 segments were the most frequently used, whereas VH4-34 was found only in non-functional or heavily mutated VDJH rearrangements. DH2 and DH3 family members were over-represented in both VDJH and DJH repertoires, while the DH1 family was under-represented only in the productive VDJH rearrangements. Finally, DH3-22 and DH2-21 gene segments were found to be over-represented in the functional repertoire while segments commonly used by less mature B-cell malignancies, such as DH6-19 or DH3-3, were under-represented.


CONCLUSIONS
Data reported here help to identify the clonogenic MM cell as a post-germinal center B cell that has undergone selection processes during the germinal center reaction.
Hematology Service, University Hospital of Salamanca and Center for Cancer Research, University of Salamanca, Spain.
David
D
González
Marcos
M
González
Ana
A
Balanzategui
Maria E
ME
Sarasquete
Ricardo
R
López-Pérez
M Carmen
MC
Chillón
Ramón
R
García-Sanz
Jesús F
JF
San Miguel
D000916:Antibody Diversity; D001402:B-Lymphocytes; D005192:Family Health; D015321:Gene Rearrangement; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D005803:Genes, Immunoglobulin / Q000235:genetics*; D006801:Humans; D007133:Immunoglobulin Joining Region; D007135:Immunoglobulin Variable Region; D009101:Multiple Myeloma / Q000235:genetics* / Q000276:immunology; D009692:Nucleic Acid Heteroduplexes / Q000737:chemistry; D016133:Polymerase Chain Reaction
D007133:Immunoglobulin Joining Region; D007135:Immunoglobulin Variable Region; D009692:Nucleic Acid Heteroduplexes