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Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 2000 Dec;91(12):1233–1240. doi: 10.1111/j.1349-7006.2000.tb00909.x

The Characteristics of Epstein‐Barr Virus (EBV)‐positive Diffuse Large B‐Cell Lymphoma: Comparison between EBV+ and EBV‐ Cases in Japanese Population

Tetuo Kuze 1,2,✉, Naoya Nakamura 1, Yuko Hashimoto 1, Yoshikazu Sasaki 1, Masafumi Abe 1
PMCID: PMC5926305  PMID: 11123421

Abstract

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 EBVencoded 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‐GCB cells, and EBV+ DLBCL frequently have a non‐functional IgH gene owing to crippling mutation.

Keywords: Epstein‐Barr virus, Diffuse large B‐cell lymphoma, Immunoglobulin heavy chain genes, Somatic mutation

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