Open AccessPrimary Malignant Lymphoma of the Brain: Mutation Pattern of Rearranged Immunoglobulin Heavy Chain Gene
Author(s) -
Endo Sumio,
Zhang ShuJing,
Saito Takafumi,
Kouno Mitsuo,
Kuroiwa Toshihiko,
Washiyama Kazuo,
Kumanishi Toshiro
Publication year - 2002
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.2002.tb01239.x
Subject(s) - biology , immunoglobulin heavy chain , somatic hypermutation , microbiology and biotechnology , immunoglobulin light chain , germinal center , mutation , lymphoma , gene rearrangement , polymerase chain reaction , somatic cell , antibody , complementarity determining region , gene , b cell , genetics , immunology
Using reverse transcription‐polymerase chain reaction (RT‐PCR), six primary brain lymphomas, pathologically diagnosed as diffuse large B‐cell lymphoma, were examined for rearranged V H ‐D‐J H 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 V H 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.