The characteristics of Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma: comparison between EBV(+) and EBV(-) cases in Japanese population.
We have investigated 114 cases with diffuse large B-cell lymphoma (DLBCL) to clarify the characteristics of DLBCL with Epstein-Barr virus (EBV) infection. Thirteen cases (11.4%) showed EBV-encoded RNA 1 (EBER1) signals by RNA in situ hybridization. EBV-encoded latent membrane protein 1 (LMP1) and EBV-encoded nuclear antigen 2 (EBNA2) were expressed in 11 and 4 cases, respectively. Expression of CD30, Bcl-6 and immunoglobulin (Ig) was found in 92%, 31% and 23% with EBV(+) DLBCL, and in 15%, 79% and 82% with EBV(-) DLBCL, respectively. The sequence of rearranged Ig heavy chain (IgH) variable (V) region gene was analyzed in 5 cases with EBV(+) DLBCL and 61 cases with EBV(-) DLBCL. Somatic mutation was found in all cases except one with EBV(-) DLBCL. Average mutation frequency was 9.6% in EBV(+) DLBCL vs. 11.5% in EBV(-) DLBCL. The rates of replacement mutation vs. silent mutation (R / S values) in complementarity determining region II and framework region III were 2.7 and 1.5 in EBV(+) DLBCL, 2.6 and 1.4 in EBV(-) DLBCL. Crippling mutation generating a stop codon was found in 2 of 5 cases (40%) with EBV(+) DLBCL, but none of 61 cases (0%) with EBV(-) DLBCL. These findings suggest that EBV(+) DLBCL and EBV(-) DLBCL were both derived from germinal center (GC) or post-GC B cells, and EBV(+) DLBCL frequently have a non-functional IgH gene owing to crippling mutation.
Kuze
T
T
First Department of Pathology, Fukushima Medical University, Fukushima 960-1295, Japan. kuze.tetsuo@toaeiyo.ne.jp
Nakamura
N
N
Hashimoto
Y
Y
Sasaki
Y
Y
Abe
M
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000032:analysis; D044466:Asian People; D001483:Base Sequence; D002648:Child; D005260:Female; D005803:Genes, Immunoglobulin; D004854:Herpesvirus 4, Human / Q000302:isolation & purification*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D016130:Immunophenotyping; D007564:Japan; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000821:virology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011379:Prognosis; D015996:Survival Rate
D015703:Antigens, CD; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region