BCL6 (B-Cell Lymphoma 6)

Identity

Other names	LAZ3 ( Lymphoma Associated Zinc finger on chromosome 3)
	ZNF51 (Zinc Finger Protein 51)
Hugo	BCL6
Location	3q27
Local_order	gene orientation: telomere - 5' LAZ3 3' - centromere
	BCL6 (3q27) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics. Laboratories willing to validate the probes are welcome : contact rocchi@biologia.uniba.it

DNA/RNA

Description	The gene is encoded by 11 exons that are located on Chromosome 3q27 and is 24.3 kb. The 5¹ portion encodes for the BTB/POZ domain (broad-complex/tramtrack/bric-a-brac/pox virus/zinc finger), while the 3¹ end encodes for 6 DNA binding zinc fingers. The first ATG occurs in exon 3.
Transcription	3.8 kb mRNA

Protein

Description	The protein product is 706 amino acids with an estimated molecular weight of 78.8 kDa.
Expression	Normally expressed in germinal center B and T cells,other lymphoid tissues, in skeletal muscle cells and in keratinocytes.
Localisation	Nuclear paraspeckles/dots
Function	The protein can bind to sequence specific DNA and repress its transcription in addition to recruiting other protein repressors. The DNA binding is mediated through the consensus sequence: TTCCT(A/C)GAA while the protein-protein interactions are mediated through the BTB/POZ domain and it has been shown to interact with other zinc finger proteins and corepressors (including Histone Deacetylase 1 (HDAC1)and Silencing Mediator of Retinoid and Thryoid Receptor 1 (SMRT1)). The carboxy terminus, on the other hand, is responsible for sequence specific DNA binding through its 6 zinc fingers.
Homology	BTB/POZ - Zinc Finger proteins (PLZF, HIC1, KUP, BAZF, ttk (drosophila), BrC (drosophila)...).

Implicated in

Entity	3q27 rearrangements /NHL (non Hodgkin lymphomas)
Disease	B cell non-Hodgkin Lymphoma (B-NHL) carry the greatest number of translocations involving the BCL6 gene locus. Translocations are most commonly detected within 15-40% of Diffuse Large B-Cell Lymphomas (DLBCL), 6-15% of Follicular Lymphomas (FL), and 50% of nodular lymphocyte predominant Hodgkin Lymphomas.
Prognosis	Generally considered to be a better prognosis if there is increased expression of BCL6. The mechanism by which its expression is increased does not seem to matter (ie different translocation partners increasing its expression results in the same prognosis).
Cytogenetics	3q27 rearrangements/aberrations are diverse and include: translocations, micro-deletions, point mutations and hypermutation. Approximately 50% of 3q27 translocations involves Ig genes at 14q32 (IgH), 2p12 (IgK) and 22q12 (IgL) (e.g. t(3;14)(q27;q32). Less than half (~40%) include a variety of other chromosomal regions (1q21, 2q21, 4p11, 5q31, 6p21, 7p12, 8q24, 9p13, 11q13, 11q23, 12q11, 13q14-21, 14q11, 15q21; 16p11...). In addition, there are frequent bi-allelic alterations (translocation and deletion or mutation on the non-translocated allele).
Hybrid/Mutated Gene	hybrid gene and transcripts are formed following promoter substitution between BCL6 and its different partners. Chimeric transcripts are generally detected containing the 5' part of the gene partner fused to the normal BCL6 exon 2 splice acceptor site. In some cases reciprocal chimeric transcripts driven by the 5' regulatory region of BCL6 fused to the partner gene coding region, have been characterised. t(2;3)(p12;q27) the gene in 2p12 is IGK t(3;3)(q25;q27) the gene in 3q25 is MBNL1 t(3;3)(q27;q27) the gene in 3q27 is ST6GAL1 t(3;3)(q27;q27) the gene in 3q27 is EIF4A2 t(3;3)(q27;q29) the gene in 3q29 is TFRC t(3;4)(q27;p13) the gene in 4p13 is RHOH t(3;6)(q27;p22) the gene in 6p22 is HIST1H4I t(3;6)(q27;p21) the gene in 6p21 is PIM1 t(3;6)(q27;p21) the gene in 6p21 is SFRS3 t(3;6)(q27;p21) the gene in 6p21 isHistone H4 t(3;6)(q27;p12) the gene in 6p12 is HSP90AB1 t(3;6)(q27;q15) the gene in 6q15 is SNHG5 t(3;7)(q27;p12) the gene in 7p12 is IKZF1 t(3;8)(q27;q24.1) the gene in 8q24.1 is MYC t(3;9)(q27;p11) the gene in 9p11 is GRHPR t(3;11)(q27;q23) the gene in 11q23 is POU2AF1 t(3;12)(q27;p13) the gene in 12p13 is GAPDH t(3;12)(q27;q12) the gene in 12q12 is LRMP t(3;12)(q27;q23) the gene in 12q23 is NACA t(3;13)(q27;q14) the gene in 13q14 is LCP1 t(3;14)(q27;q32) the gene in 14q32 is IGH t(3;14)(q27;q32) the gene in 14q32 is HSP90AA1 t(3;16)(q27;p13) the gene in 16p13 is CIITA t(3;16)(q27;p11) the gene in 16p11 is IL21R t(3;19)(q27;q13) the gene in 19q13 is NAPA t(3;22)(q27;q11) the gene in 22q11 is IGL
Abnormal Protein	no fusion protein

Breakpoints

Note	Clustered in a 3,3kb EcoRI fragment (MTC) includind exon 1A and intron 1.

External links

	Nomenclature
Hugo	BCL6
GDB	BCL6
Entrez_Gene	BCL6  604  B-cell CLL/lymphoma 6 (zinc finger protein 51)
	Cards
Atlas	BCL6ID20
GeneCards	BCL6
Ensembl	BCL6 [Search_View]   ENSG00000113916 [Gene_View]
Genatlas	BCL6
GeneLynx	BCL6
eGenome	BCL6
euGene	604
	Genomic and cartography
GoldenPath	BCL6  -  3q27   chr3:188921859-188936942 -  3q27   [Description]    (hg18-Mar_2006)
Ensembl	BCL6 - 3q27 [CytoView]
NCBI	Mapview
OMIM	Disease map [OMIM]
HomoloGene	BCL6
	Gene and transcription
Genbank	AI624861 [ ENTREZ ]
Genbank	BC142705 [ ENTREZ ]
Genbank	BC146796 [ ENTREZ ]
Genbank	BC150184 [ ENTREZ ]
Genbank	BX649185 [ ENTREZ ]
RefSeq	NM_001706 [ SRS ]    NM_001706 [ ENTREZ ]
RefSeq	NM_138931 [ SRS ]    NM_138931 [ ENTREZ ]
RefSeq	AC_000046 [ SRS ]    AC_000046 [ ENTREZ ]
RefSeq	NC_000003 [ SRS ]    NC_000003 [ ENTREZ ]
RefSeq	NT_005612 [ SRS ]    NT_005612 [ ENTREZ ]
RefSeq	NW_921807 [ SRS ]    NW_921807 [ ENTREZ ]
AceView	BCL6 AceView - NCBI
Unigene	Hs.478588 [ SRS ]    Hs.478588 [ NCBI ]     HS478588 [ spliceNest ]
Fast-db	15492 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	P41182 [ SRS]    P41182 [ EXPASY ]     P41182 [ INTERPRO ]
Prosite	PS50097 BTB [ SRS ]    PS50097 BTB [ Expasy ]
Prosite	PS00028 ZINC_FINGER_C2H2_1 [ SRS ]    PS00028 ZINC_FINGER_C2H2_1 [ Expasy ]
Prosite	PS50157 ZINC_FINGER_C2H2_2 [ SRS ]    PS50157 ZINC_FINGER_C2H2_2 [ Expasy ]
Interpro	IPR000210 BTB/POZ-like [ SRS ]    IPR000210 BTB/POZ-like [ EBI ]
Interpro	IPR011333 BTB/POZ_fold [ SRS ]    IPR011333 BTB/POZ_fold [ EBI ]
Interpro	IPR013069 BTB_POZ [ SRS ]    IPR013069 BTB_POZ [ EBI ]
Interpro	IPR007087 Znf_C2H2 [ SRS ]    IPR007087 Znf_C2H2 [ EBI ]
Interpro	IPR015880 Znf_C2H2-like [ SRS ]    IPR015880 Znf_C2H2-like [ EBI ]
Interpro	IPR013087 Znf_C2H2/integrase_DNA-bd [ SRS ]    IPR013087 Znf_C2H2/integrase_DNA-bd [ EBI ]
CluSTr	P41182
Pfam	PF00651 BTB [ SRS ]    PF00651 BTB [ Sanger ]    pfam00651 [ NCBI-CDD ]
Pfam	PF00096 zf-C2H2 [ SRS ]    PF00096 zf-C2H2 [ Sanger ]    pfam00096 [ NCBI-CDD ]
Smart	SM00225 BTB [EMBL]
Smart	SM00355 ZnF_C2H2 [EMBL]
Blocks	P41182
PDB	1R28 [ SRS ]    1R28 [ PdbSum ],   1R28 [ IMB ]   1R28 [ RSDB ]
PDB	1R29 [ SRS ]    1R29 [ PdbSum ],   1R29 [ IMB ]   1R29 [ RSDB ]
PDB	1R2B [ SRS ]    1R2B [ PdbSum ],   1R2B [ IMB ]   1R2B [ RSDB ]
PDB	2EN2 [ SRS ]    2EN2 [ PdbSum ],   2EN2 [ IMB ]   2EN2 [ RSDB ]
PDB	2EOS [ SRS ]    2EOS [ PdbSum ],   2EOS [ IMB ]   2EOS [ RSDB ]
HPRD	00180
	Protein Interaction databases
DIP	P41182
IntAct	P41182
	Polymorphism : SNP, mutations, diseases
OMIM	109565    [ map ]
GENECLINICS	109565
SNP	BCL6 [dbSNP-NCBI]
SNP	NM_001706 [SNP-NCI]
SNP	NM_138931 [SNP-NCI]
SNP	BCL6 [GeneSNPs - Utah]  BCL6] [HGBASE - SRS]
HAPMAP	BCL6 [HAPMAP]
COSMIC	BCL6 [Somatic mutation (COSMIC-CGP-Sanger)]
TICdb	BCL6 [Translocation breakpoints In Cancer]
HGMD	BCL6
	General knowledge
Family Browser	BCL6 [UCSC Family Browser]
SOURCE	NM_001706
SOURCE	NM_138931
SMD	Hs.478588
SAGE	Hs.478588
GO	protein import into nucleus, translocation [Amigo]  protein import into nucleus, translocation
GO	negative regulation of transcription from RNA polymerase II promoter [Amigo]  negative regulation of transcription from RNA polymerase II promoter
GO	cell morphogenesis [Amigo]  cell morphogenesis
GO	negative regulation of cell-matrix adhesion [Amigo]  negative regulation of cell-matrix adhesion
GO	regulation of germinal center formation [Amigo]  regulation of germinal center formation
GO	negative regulation of T-helper 2 type immune response [Amigo]  negative regulation of T-helper 2 type immune response
GO	negative regulation of B cell apoptosis [Amigo]  negative regulation of B cell apoptosis
GO	DNA binding [Amigo]  DNA binding
GO	chromatin binding [Amigo]  chromatin binding
GO	protein binding [Amigo]  protein binding
GO	intracellular [Amigo]  intracellular
GO	nucleus [Amigo]  nucleus
GO	nucleus [Amigo]  nucleus
GO	replication fork [Amigo]  replication fork
GO	transcription [Amigo]  transcription
GO	regulation of transcription, DNA-dependent [Amigo]  regulation of transcription, DNA-dependent
GO	response to DNA damage stimulus [Amigo]  response to DNA damage stimulus
GO	Rho protein signal transduction [Amigo]  Rho protein signal transduction
GO	spermatogenesis [Amigo]  spermatogenesis
GO	protein localization [Amigo]  protein localization
GO	zinc ion binding [Amigo]  zinc ion binding
GO	negative regulation of cell proliferation [Amigo]  negative regulation of cell proliferation
GO	transcription repressor activity [Amigo]  transcription repressor activity
GO	transcription repressor activity [Amigo]  transcription repressor activity
GO	actin cytoskeleton organization and biogenesis [Amigo]  actin cytoskeleton organization and biogenesis
GO	B cell differentiation [Amigo]  B cell differentiation
GO	negative regulation of cell growth [Amigo]  negative regulation of cell growth
GO	positive regulation of B cell proliferation [Amigo]  positive regulation of B cell proliferation
GO	regulation of Rho GTPase activity [Amigo]  regulation of Rho GTPase activity
GO	negative regulation of mast cell cytokine production [Amigo]  negative regulation of mast cell cytokine production
GO	negative regulation of Rho protein signal transduction [Amigo]  negative regulation of Rho protein signal transduction
GO	T-helper 2 type immune response [Amigo]  T-helper 2 type immune response
GO	positive regulation of apoptosis [Amigo]  positive regulation of apoptosis
GO	regulation of memory T cell differentiation [Amigo]  regulation of memory T cell differentiation
GO	sequence-specific DNA binding [Amigo]  sequence-specific DNA binding
GO	negative regulation of cell differentiation [Amigo]  negative regulation of cell differentiation
GO	negative regulation of T-helper 2 cell differentiation [Amigo]  negative regulation of T-helper 2 cell differentiation
GO	negative regulation of S phase of mitotic cell cycle [Amigo]  negative regulation of S phase of mitotic cell cycle
GO	metal ion binding [Amigo]  metal ion binding
GO	negative regulation of isotype switching to IgE isotypes [Amigo]  negative regulation of isotype switching to IgE isotypes
GO	erythrocyte development [Amigo]  erythrocyte development
GO	regulation of inflammatory response [Amigo]  regulation of inflammatory response
GO	regulation of immune response [Amigo]  regulation of immune response
GO	positive regulation of cell motility [Amigo]  positive regulation of cell motility
PubGene	BCL6
TreeFam	BCL6
CTD	604 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	BCL6 Related clones (RZPD - Berlin)
	PubMed
PubMed	108 Pubmed reference(s) in LocusLink

Bibliography

LAZ3, a novel zinc-finger encoding gene, is disrupted by recurring chromosome 3q27 translocations in human lymphomas.

Kerckaert JP, Deweindt C, Tilly H, Quief S, Lecocq G, Bastard C

Nature genetics. 1993 ; 5 (1) : 66-70.

PMID 8220427

Alterations of a zinc finger-encoding gene, BCL-6, in diffuse large-cell lymphoma.

Ye BH, Lista F, Lo Coco F, Knowles DM, Offit K, Chaganti RS, Dalla-Favera R

Science (New York, N.Y.). 1993 ; 262 (5134) : 747-750.

PMID 8235596

Gene involved in the 3q27 translocation associated with B-cell lymphoma, BCL5, encodes a Krˆºppel-like zinc-finger protein.

Miki T, Kawamata N, Hirosawa S, Aoki N

Blood. 1994 ; 83 (1) : 26-32.

PMID 8274740

High BCL6 expression predicts better prognosis, independent of BCL6 translocation status, translocation partner, or BCL6-deregulating mutations, in gastric lymphoma.

Chen YW, Hu XT, Liang AC, Au WY, So CC, Wong ML, Shen L, Tao Q, Chu KM, Kwong YL, Liang RH, Srivastava G

Blood. 2006 ; 108 (7) : 2373-2383.

PMID 16772602

Intrachromosomal rearrangement of chromosome 3q27: an under recognized mechanism of BCL6 translocation in B-cell non-Hodgkin lymphoma.

Keller CE, Nandula S, Vakiani E, Alobeid B, Murty VV, Bhagat G

Human pathology. 2006 ; 37 (8) : 1093-1099.

PMID 16867873

Prognostic impact of chromosomal alteration of 3q27 on nodal B-cell lymphoma: correlation with histology, immunophenotype, karyotype, and clinical outcome in 329 consecutive patients.

Niitsu N, Okamoto M, Nakamura N, Nakamine H, Aoki S, Hirano M, Miura I

Leukemia research. 2007 ; 31 (9) : 1191-1197.

PMID 17197022

Pathogenetic and clinical implications of non-immunoglobulin ; BCL6 translocations in B-cell non-Hodgkin's lymphoma.

Ohno H

Journal of clinical and experimental hematopathology : JCEH. 2006 ; 46 (2) : 43-53.

PMID 17142954

A novel t(2;3)(p11;q27) in a case of follicular lymphoma.

Tapinassi C, Micucci C, Lahortiga I, Malazzi O, Gasparini P, Gorosquieta A, Odero MD, Belloni E

Cancer genetics and cytogenetics. 2007 ; 172 (1) : 70-73.

PMID 17175383

A novel t(3;8)(q27;q24.1) simultaneously involving both the BCL6 and MYC genes in a diffuse large B-cell lymphoma.

Wang HY, Bossler AD, Schaffer A, Tomczak E, DiPatri D, Frank DM, Nowell PC, Bagg A

Cancer genetics and cytogenetics. 2007 ; 172 (1) : 45-53.

PMID 17175379

REVIEW articles	automatic search in PubMed
Last year publications	automatic search in PubMed

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Contributor(s)

Written	09-1998	Jean-Pierre Kerkaert
		Unité 124 INSERM, Institut de Recherches sur le Cancer, Place de Verdun, 59045 Lille cedex, France

Citation

This paper should be referenced as such :

Kerkaert JP . BCL6 (B-Cell Lymphoma 6). Atlas Genet Cytogenet Oncol Haematol. September 1998 . URL : http://AtlasGeneticsOncology.org/Genes/BCL6ID20.html

Knezevich S . BCL6 (B-Cell Lymphoma 6). Atlas Genet Cytogenet Oncol Haematol. . URL : http://AtlasGeneticsOncology.org/Genes/BCL6ID20.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Wed Jul 2 08:22:10 2008