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

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

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)339-344
Number of pages6
JournalPathology International
Volume63
Issue number7
DOIs
Publication statusPublished - Jul 2013

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Immunoglobulin Heavy Chain Genes
Lymphoma, Large B-Cell, Diffuse
Mutation
Immunoglobulin Genes
B-Lymphocytes
Leucine Zippers
Germinal Center
B-Cell Lymphoma
Genetic Recombination

Keywords

  • BACH2
  • Diffuse large B-cell lymphoma
  • Immunoglobulin gene
  • Immunohistochemistry

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

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. / Kikuchi, Tomoki; Tokunaka, Mami; Kikuti, Yara Yukie; Carreras, Joaquim; Ogura, Go; Takekoshi, Susumu; Kojima, Minoru; Ando, Kiyoshi; Hashimoto, Yuko; Abe, Masafumi; Takata, Katsuyoshi; Yoshino, Tadashi; Muto, Akihiko; Igarashi, Kazuhiko; Nakamura, Naoya.

In: Pathology International, Vol. 63, No. 7, 07.2013, p. 339-344.

Research output: Contribution to journalArticle

Kikuchi, T, Tokunaka, M, Kikuti, YY, Carreras, J, Ogura, G, Takekoshi, S, Kojima, M, Ando, K, Hashimoto, Y, Abe, M, Takata, K, Yoshino, T, Muto, A, Igarashi, K & Nakamura, N 2013, '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', Pathology International, vol. 63, no. 7, pp. 339-344. https://doi.org/10.1111/pin.12076
Kikuchi, Tomoki ; Tokunaka, Mami ; Kikuti, Yara Yukie ; Carreras, Joaquim ; Ogura, Go ; Takekoshi, Susumu ; Kojima, Minoru ; Ando, Kiyoshi ; Hashimoto, Yuko ; Abe, Masafumi ; Takata, Katsuyoshi ; Yoshino, Tadashi ; Muto, Akihiko ; Igarashi, Kazuhiko ; Nakamura, Naoya. / 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. In: Pathology International. 2013 ; Vol. 63, No. 7. pp. 339-344.
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AU - Kikuchi, Tomoki

AU - Tokunaka, Mami

AU - Kikuti, Yara Yukie

AU - Carreras, Joaquim

AU - Ogura, Go

AU - Takekoshi, Susumu

AU - Kojima, Minoru

AU - Ando, Kiyoshi

AU - Hashimoto, Yuko

AU - Abe, Masafumi

AU - Takata, Katsuyoshi

AU - Yoshino, Tadashi

AU - Muto, Akihiko

AU - Igarashi, Kazuhiko

AU - Nakamura, Naoya

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N2 - 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.

AB - 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.

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