Chromosomal translocations cause deregulated BCL6 expression by promoter substitution in B cell lymphoma Journal Article
| Authors: | Ye, B. H.; Chaganti, S.; Chang, C. C.; Niu, H.; Corradini, P.; Chaganti, R. S. K.; Dalla-Favera, R. |
| Article Title: | Chromosomal translocations cause deregulated BCL6 expression by promoter substitution in B cell lymphoma |
| 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. |
| Keywords: | controlled study; human tissue; gene cluster; human cell; promoter region; exon; dna-binding proteins; proto-oncogene proteins; case report; allele; gene expression; gene locus; intron; alleles; transcription factor; tumor cells, cultured; transcription factors; chimera; rna; cloning, molecular; gene mapping; germ line; b cell lymphoma; gene expression regulation, neoplastic; lymphoma, b-cell; immunoglobulin heavy chain; molecular sequence data; tumor cell line; dna, neoplasm; lymphoma; chromosome breakage; chromosome rearrangement; base sequence; translocation, genetic; dna primers; zinc finger protein; dna transcription; complementary dna; dna, complementary; chromosomes, human, pair 3; zinc fingers; chromosomal translocation; promoter regions (genetics); proto-oncogene proteins c-bcl-6; lymphoma, large-cell, diffuse; chromosomes, human, pair 14; genes, immunoglobulin; bcl6; humans; human; priority journal; article; chromosome translocation 3; immunoglobulin genes |
| Journal Title: | EMBO Journal |
| Volume: | 14 |
| Issue: | 24 |
| ISSN: | 0261-4189 |
| Publisher: | Wiley Blackwell |
| Date Published: | 1995-12-15 |
| Start Page: | 6209 |
| End Page: | 6217 |
| Language: | English |
| PUBMED: | 8557040 |
| PROVIDER: | scopus |
| PMCID: | PMC394745 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 28 August 2018 -- Source: Scopus |
Citation Impact
Related MSK Work