Immunoglobulin gene rearrangement analysis in composite hodgkin disease and large B-cell lymphoma: evidence for receptor revision of immunoglobulin heavy chain variable region genes in Hodgkin-Reed-Sternberg cells?
Immunoglobulin heavy chain gene (IgH) rearrangement was studied in a patient showing the occurrence of classical Hodgkin disease and large B-cell lymphoma (LBCL) in the same lymph node. The VHDHJH region was amplified by polymerase chain reaction, the template being the DNA extracted from single Hodgkin and Reed-Sternberg and LBCL cells, microdissected on hematoxylin-eosin-stained sections by laser capture. A repeated VH4DH3JH4 segment was found in Reed-Sternberg cells, whereas a repeated VH3DH3JH4 segment was observed in LBCL cells. Rearranged VH genes carried somatic mutations in both populations, indicating a common germinal center cell origin. The IgH rearrangement found in clonally related Reed-Sternberg cells differed from the one of LBCL cells in the VH region but showed the same JH and DH segments with no variation from the respective germline sequence. The DH-JH junction is the first immunoglobulin gene segment rearranged in precursor B cells. Because the possibility of secondary Ig gene rearrangement in peripheral lymphoid organs has recently been reported, in the patient described here Reed-Sternberg and LBCL cells might originate from a common precursor in which secondary VH replacement took place during the germinal center reaction, giving rise to two different clonally related lymphomas.
Bellan
Cristiana
C
Institute of Pathologic Anatomy and Histopathology, University of Siena, Italy.
Lazzi
Stefano
S
Zazzi
Maurizio
M
Lalinga
Anna Vittoria
AV
Palummo
Nazareno
N
Galieni
Piero
P
Marafioti
Teresa
T
Tonini
Tiziana
T
Cinti
Caterina
C
Leoncini
Lorenzo
L
Pileri
Stefano A
SA
Tosi
Piero
P
D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain / Q000235:genetics*; D006689:Hodgkin Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics* / Q000378:metabolism; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009154:Mutation; D016133:Polymerase Chain Reaction; D011947:Receptors, Antigen, B-Cell / Q000235:genetics* / Q000378:metabolism; D016539:Reed-Sternberg Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D017422:Sequence Analysis, DNA
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D007135:Immunoglobulin Variable Region; D011947:Receptors, Antigen, B-Cell