Mutational analysis of IgVH and BCL-6 genes suggests thymic B-cells origin of mediastinal (thymic) B-cell lymphoma.
Mediastinal (thymic) large B-cell lymphoma (MBL) has been defined as a subtype of diffuse large B-cell lymphoma (DLBL) arising in the mediastinum with characteristic clinicopathological features. It has been postulated that MBL arise from non-circulating thymic B-cells and represent a distinct lymphoma entity, however, the histogenesis of the disease is not yet fully understood. In order to clarify the histogenetic derivation of MBL and to determine the relationship of MBL to thymic B-cells we have analyzed the nucleic acid sequences of immunoglobulin (Ig) heavy chain variable region (VH) and 5' noncoding region of BCL-6 genes in normal thymic B-cells and six cases of MBL. Thymic B-cells and tumor cells of MBLs displayed hypermutated VH and/or BCL-6 genes but intraclonal divergence did not associate with these mutations. Since somatic mutations of the IgVH and BCL-6 genes are histogenetic markers of B-cell transit through the germinal centre (GC), these results suggest that both thymic B-cells and MBLs derived from GC or an equivalent environment where B-cells underwent somatic hypermutation. The similar pattern of mutations of IgVH and BCL-6 genes found in thymic B-cells and MBLs further supports the theory that MBLs originate from thymic B-cells.
Csernus
Balázs
B
1st Department of Pathology and Experimental Cancer Research, Faculty of Medicine, Semmelweis University, H-1085 Budapest, Ullöi út 26, Hungary.
Timár
Botond
B
Fülöp
Zsolt
Z
Bognár
Agnes
A
Szepesi
Agota
A
László
Terézia
T
Jáksó
Pál
P
Warnke
Roger
R
Kopper
László
L
Matolcsy
András
A
D000328:Adult; D001402:B-Lymphocytes / Q000473:pathology; D019070:Cell Lineage; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005803:Genes, Immunoglobulin / Q000235:genetics*; D018858:Germinal Center; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000473:pathology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000473:pathology; D008297:Male; D008479:Mediastinal Neoplasms / Q000235:genetics / Q000473:pathology*; D008875:Middle Aged; D051560:Proto-Oncogene Proteins c-bcl-6; D027041:Somatic Hypermutation, Immunoglobulin; D013950:Thymus Gland / Q000473:pathology*
C084103:BCL6 protein, human; D004268:DNA-Binding Proteins; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D051560:Proto-Oncogene Proteins c-bcl-6