title: 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.
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.
authors.affiliation: Department of Pathology, Tokai University School of Medicine, Isehara, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Kikuchi
authors.forename: Mami
authors.initials: M
authors.lastname: Tokunaka
authors.forename: Yara Yukie
authors.initials: YY
authors.lastname: Kikuti
authors.forename: Joaquim
authors.initials: J
authors.lastname: Carreras
authors.forename: Go
authors.initials: G
authors.lastname: Ogura
authors.forename: Susumu
authors.initials: S
authors.lastname: Takekoshi
authors.forename: Minoru
authors.initials: M
authors.lastname: Kojima
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ando
authors.forename: Yuko
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: Masafumi
authors.initials: M
authors.lastname: Abe
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Takata
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yoshino
authors.forename: Akihiko
authors.initials: A
authors.lastname: Muto
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Igarashi
authors.forename: Naoya
authors.initials: N
authors.lastname: Nakamura
mesh_terms: D001483:Base Sequence; D050976:Basic-Leucine Zipper Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics* / Q000378:metabolism; D007135:Immunoglobulin Variable Region / Q000235:genetics* / Q000378:metabolism; D007150:Immunohistochemistry; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics*
chemical_list: C491123:BACH2 protein, human; D050976:Basic-Leucine Zipper Transcription Factors; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region
keywords: BACH2; diffuse large B-cell lymphoma; immunoglobulin gene; immunohistochemistry