Low incidence of mbr bcl-2/JH fusion genes in Hodgkin's disease.
Lymph node biopsies from 140 cases of Hodgkin's disease (HD) and from 30 non-malignant lesions were screened for the presence of t(14;18) translocations involving the major breakpoint region (mbr) of the bcl-2 gene and the joining region (JH) of the immunoglobulin heavy chain gene, using a polymerase chain reaction (PCR) assay with subsequent nucleotide sequencing of amplified bcl-2/JH junctional regions. Expression of the bcl-2 protein within the Hodgkin and Reed-Sternberg (HRS) cells was investigated in 86 cases of HD by immunohistochemistry on cryostat or paraffin sections. Although bcl-2 expression could be found in a proportion of neoplastic cells in up to one-third of HD cases, the frequency of t(14;18) gene fusions detected by PCR was low. We identified such gene fusions in only 3 out of 140 (2 per cent) HD cases, one biopsy of which presented with four clonally distinct bcl-2/JH sequences. No t(14;18) was found in any of 30 reactive lymph node lesions. All fusion gene sequences were unique regarding the localization of the chromosome 14 and 18 breakpoints and the extranucleotide N-insertions. None of these gene fusions conformed to t(14;18) breakpoint sequences previously characterized in our laboratories. Our findings point to a mere coincidence in some cases of HD lesions and cells carrying a t(14;18) in the same biopsy and argue against a significant role of bcl-2 in the pathogenesis of HD.
Kneba
M
M
Department of Internal Medicine, Georg-August-University, Göttingen, Germany.
Eick
S
S
Herbst
H
H
Pott
C
C
Bolz
I
I
Dallenbach
F
F
Hiddemann
W
W
Stein
H
H
D001483:Base Sequence; D015139:Blotting, Southern; D002883:Chromosomes, Human, Pair 14; D002887:Chromosomes, Human, Pair 18; D005803:Genes, Immunoglobulin; D006689:Hodgkin Disease / Q000235:genetics*; D006801:Humans; D007144:Immunoglobulin J-Chains / Q000235:genetics*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2; D014178:Translocation, Genetic
D007144:Immunoglobulin J-Chains; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2