Chromosomal translocations cause deregulated BCL6 expression by promoter substitution in B cell lymphoma

B. Hilda Ye, Seeta Chaganti, Chih Chao Chang, Huifeng Niu, Paolo Corradini, R. S K Chaganti, Riccardo Dalla-Favera

Research output: Contribution to journalArticle

237 Citations (Scopus)

Abstract

The BCL6 gene codes for a zinc-finger transcription factor and is involved in chromosomal rearrangements in 30-40% of diffuse large-cell lymphoma (DLCL). These rearrangements cluster within the 5' regulatory region of BCL6 spanning its first non-coding exon. To determine the functional consequences of these alterations, we have analyzed the structure of the rearranged BCL6 alleles and their corresponding RNA and protein species in two DLCL biopsies and one tumor cell line which carried the t(3;14)(q27;q32) translocation involving the BCL6 and immunoglobulin heavy-chain (IgH) loci. In all three cases, the breakpoints were mapped within the IgH switch region and the BCL6 first intron, leading to the juxtaposition of part of the IgH locus upstream and in the same transcriptional orientation to the BCL6 coding exons. An analysis of cDNA clones showed that these recombinations generate chimeric IgH-BCL6 transcripts which initiated from IgH germline transcript promoters (I(μ) or I(γ)3), but retain a normal BCL6 coding domain. In the tumor cell line, the chimeric I(γ)3-BCL6 allele, but not the germline BCL6 gene, was transcriptionally active and produced a normal BCL6 protein. These findings indicate that t(3;14) translocations alter BCL6 expression by promoter substitution and imply that the consequence of these alterations is the deregulated expression of a normal BCL6 protein.

Original languageEnglish (US)
Pages (from-to)6209-6217
Number of pages9
JournalEMBO Journal
Volume14
Issue number24
StatePublished - 1995
Externally publishedYes

Fingerprint

Immunoglobulin Heavy Chains
Genetic Translocation
B-Cell Lymphoma
Substitution reactions
Cells
Lymphoma, Large B-Cell, Diffuse
Tumor Cell Line
Tumors
Exons
Genes
Alleles
Proteins
Biopsy
Nucleic Acid Regulatory Sequences
Zinc Fingers
Introns
Genetic Recombination
Zinc
Transcription Factors
Complementary DNA

Keywords

  • BCL6
  • Chromosomal translocation
  • Immunoglobulin genes
  • Lymphoma
  • Zinc fingers

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Ye, B. H., Chaganti, S., Chang, C. C., Niu, H., Corradini, P., Chaganti, R. S. K., & Dalla-Favera, R. (1995). Chromosomal translocations cause deregulated BCL6 expression by promoter substitution in B cell lymphoma. EMBO Journal, 14(24), 6209-6217.

Chromosomal translocations cause deregulated BCL6 expression by promoter substitution in B cell lymphoma. / Ye, B. Hilda; Chaganti, Seeta; Chang, Chih Chao; Niu, Huifeng; Corradini, Paolo; Chaganti, R. S K; Dalla-Favera, Riccardo.

In: EMBO Journal, Vol. 14, No. 24, 1995, p. 6209-6217.

Research output: Contribution to journalArticle

Ye, BH, Chaganti, S, Chang, CC, Niu, H, Corradini, P, Chaganti, RSK & Dalla-Favera, R 1995, 'Chromosomal translocations cause deregulated BCL6 expression by promoter substitution in B cell lymphoma', EMBO Journal, vol. 14, no. 24, pp. 6209-6217.
Ye BH, Chaganti S, Chang CC, Niu H, Corradini P, Chaganti RSK et al. Chromosomal translocations cause deregulated BCL6 expression by promoter substitution in B cell lymphoma. EMBO Journal. 1995;14(24):6209-6217.
Ye, B. Hilda ; Chaganti, Seeta ; Chang, Chih Chao ; Niu, Huifeng ; Corradini, Paolo ; Chaganti, R. S K ; Dalla-Favera, Riccardo. / Chromosomal translocations cause deregulated BCL6 expression by promoter substitution in B cell lymphoma. In: EMBO Journal. 1995 ; Vol. 14, No. 24. pp. 6209-6217.
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