Primary malignant lymphoma of the brain: mutation pattern of rearranged immunoglobulin heavy chain gene.
Using reverse transcription-polymerase chain reaction (RT-PCR), six primary brain lymphomas, pathologically diagnosed as diffuse large B-cell lymphoma, were examined for rearranged VH-D-JH sequences of the immunoglobulin heavy chain gene, focusing on somatic mutations and intraclonal heterogeneity. The reliability of the isolated PCR clones was confirmed by in situ hybridization (ISH) with complementarity-determining region (CDR) 3 oligonucleotide probes. Sequence analysis of the PCR clones revealed a high frequency of somatic mutation, ranging from 8.8 to 27.3% (mean 18.2%) in the VH gene segments in all the lymphomas. A significantly lower frequency of replacement (R) mutations than expected was also seen in their frameworks (FRs) in all cases. These findings suggested that the precursor cells were germinal center (GC)-related cells in these lymphomas. However, despite extensive cloning experiments, intraclonal heterogeneity was not detected in any case except for one in which it could not be ruled out. Thus, it seemed likely that all of our brain lymphomas were derived from GC-related cells and that at least most of them were from post-GC cells.
Endo
Sumio
S
Molecular Neuropathology, Brain Research Institute, Niigata University, Niigata 951-8585, Japan.
Zhang
Shu-Jing
SJ
Saito
Takafumi
T
Kouno
Mitsuo
M
Kuroiwa
Toshihiko
T
Washiyama
Kazuo
K
Kumanishi
Toshiro
T
D000368:Aged; D001483:Base Sequence; D001932:Brain Neoplasms / Q000235:genetics* / Q000276:immunology; D005260:Female; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics; D017403:In Situ Hybridization; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction
D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region