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Over‐expression of BACH2 is related to ongoing somatic hypermutation of the immunoglobulin heavy chain gene variable region of de novo diffuse large B‐cell lymphoma
Authors:Tomoki Kikuchi  Mami Tokunaka  Yara Yukie Kikuti  Joaquim Carreras  Go Ogura  Susumu Takekoshi  Minoru Kojima  Kiyoshi Ando  Yuko Hashimoto  Masafumi Abe  Katsuyoshi Takata  Tadashi Yoshino  Akihiko Muto  Kazuhiko Igarashi  Naoya Nakamura
Affiliation:1. Department of Pathology, Tokai University School of Medicine, , Isehara, Japan;2. Department of Hematology, Tokai University School of Medicine, , Isehara, Japan;3. Department of Pathology, Fukushima Medical University School of Medicine, , Fukushima, Japan;4. Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, , Okayama, Japan;5. Department of Biochemistry, Tohoku University School of Medicine, , Sendai, Japan
Abstract:
The basic region–leucine zipper (bZip) factor BTB, CNC homology 2 (BACH2) is known to have important roles in class switch recombination and somatic hypermutation (SHM) of the immunoglobulin (Ig) gene. In this study, we investigated the relationship between the expression of BACH2 and the status of SHM of the Ig heavy chain gene variable region (IgHV) for SHM in diffuse large B‐cell lymphoma (DLBCL). We examined 20 cases of DLBCL, 13 of which were germinal center B‐cell (GCB) DLBCL and 7 were non‐GCB DLBCL. Seven cases were negative, 6 were positive (cytoplasmic expression) and 7 were strongly positive (both nuclear and cytoplasmic expression) for BACH2. Confirmed mutation (CM) was identified in 8 cases and the CM index (number of confirmed mutations per 10 subclones) was distributed from 0 to 5. A CM index of 7 strongly positive (over‐expression) cases with BACH2 were distributed from 0 to 5, and that of 7 negative and 6 positive cases were distributed from 0 to 1. Over‐expression of BACH2 was statistically related to CM index (P = 0.008). In conclusion, over‐expression of BACH2 is critical for ongoing SHM of IgHV in DLBCL, and our data suggest that BACH2 may play an essential role for SHM of the Ig gene in B‐cell lymphoma.
Keywords:BACH2  diffuse large B‐cell lymphoma  immunoglobulin gene  immunohistochemistry
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