title: Identification of IGHCδ-BACH2 fusion transcripts resulting from cryptic chromosomal rearrangements of 14q32 with 6q15 in aggressive B-cell lymphoma/leukemia.
abstract: In B-cell malignancies, genes implicated in B-cell differentiation, germinal center formation, apoptosis, and cell cycle regulation are juxtaposed to immunoglobulin loci through chromosomal translocations. In this study, we identified the BTB and CNC homology 2 (BACH2) gene as a novel translocation partner of the immunoglobulin heavy chain (IGH) locus in a patient with IGH-MYC-positive, highly aggressive B-cell lymphoma/leukemia carrying der(14)t(8;14) and del(6)(q15). Fluorescence in situ hybridization analysis using an IGH/MYC probe detected an IGH-MYC fusion signal on der(14) and IGH signal on del(6). Genome copy number analysis showed a deletion in the 6q15-25 region and a centromeric breakpoint within the BACH2 gene. cDNA bubble polymerase chain reaction using BACH2 primers revealed that the first exon of Cδ was fused to the 5'-untranslated region of BACH2 exon 2. The Cδ-BACH2 fusion transcript consisted of exon 1 of Cδ and exons 2 to 9 of BACH2, encompassing the entire BACH2 coding region, and the BACH2 was highly expressed in this patient. These results indicate that Cδ-BACH2 fusion may cause constitutive activation of BACH2. Although additional screening of 47 samples of B-cell non-Hodgkin's lymphoma (B-NHL) patients and 29 cell lines derived from B-cell malignancies by double-color fluorescence in situ hybridization analysis detected a split signal with deletion of centromeric region of BACH2 only in a patient with follicular lymphoma, BACH2 was highly expressed in lymphoma cells of the patient and B-NHL cell lines with IGH-MYC translocation. These findings suggest that BACH2 plays a critical role in B-cell lymphomagenesis, especially related to IGH-MYC translocation in some way.
authors.affiliation: Department of Molecular Hematology and Oncology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Taki
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Chinen
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tsutsumi
authors.forename: Muneo
authors.initials: M
authors.lastname: Ohshiro
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Junya
authors.initials: J
authors.lastname: Kuroda
authors.forename: Shigeo
authors.initials: S
authors.lastname: Horiike
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nishida
authors.forename: Masafumi
authors.initials: M
authors.lastname: Taniwaki
mesh_terms: D000368:Aged; D001402:B-Lymphocytes / Q000378:metabolism; D001483:Base Sequence; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics*; D056905:Chromosome Breakpoints; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D015973:Gene Expression Regulation, Leukemic; D050939:Gene Fusion; D016259:Genes, myc; D006801:Humans; D007138:Immunoglobulin delta-Chains / Q000235:genetics*; D017404:In Situ Hybridization, Fluorescence; D007938:Leukemia / Q000235:genetics; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000473:pathology; D008297:Male; D008969:Molecular Sequence Data; D017422:Sequence Analysis, DNA; D014178:Translocation, Genetic
chemical_list: C491123:BACH2 protein, human; D050976:Basic-Leucine Zipper Transcription Factors; D004273:DNA, Neoplasm; D007138:Immunoglobulin delta-Chains