Atlas of Genetics and Cytogenetics in Oncology and Haematology

Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   
X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

BCL6 (B-Cell Lymphoma 6)

Identity

Other namesLAZ3 ( Lymphoma Associated Zinc finger on chromosome 3)
ZNF51 (Zinc Finger Protein 51)
HGNC (Hugo) BCL6
Location 3q27
Location_base_pair Starts at 187439165 and ends at 187454285 bp from pter ( according to hg19-Feb_2009)  [Mapping]
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 5' portion encodes for the BTB/POZ domain (broad-complex/tramtrack/bric-a-brac/pox virus/zinc finger), while the 3' 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
    HGNC (Hugo)BCL6   1001
    Entrez_Gene (NCBI)BCL6  604  B-cell CLL/lymphoma 6
    Cards
    AtlasBCL6ID20
    GeneCards (Weizmann)BCL6
    Ensembl (Hinxton)ENSG00000113916 [Gene_View]  BCL6 [Vega]
    AceView (NCBI)BCL6
    Genatlas (Paris)BCL6
    euGene (Indiana)604
    SOURCE (Stanford)NM_001130845 NM_001134738 NM_001706
    Gene Expression (Array Express) ENSG00000113916
    Genomic and cartography
    GoldenPath (UCSC)BCL6  -  3q27   chr3:187439165-187454285 -  3q27   [Description]    (hg19-Feb_2009)
    EnsemblBCL6 - 3q27 [CytoView]
    Mapping of homologs : NCBIBCL6 [Mapview]
    OMIM109565   
    Gene and transcription
    Gene : Genbank (Entrez)AI624861 AK304325 AK308162 AW337942 AW470156
    Reference sequence (RefSeq transcript) :SRSNM_001130845 NM_001134738 NM_001706
    Reference transcript : EntrezNM_001130845 NM_001134738 NM_001706
    RefSeq genomic : SRSAC_000046 AC_000135 NC_000003 NG_007149 NT_005612 NW_001838884 NW_921807
    RefSeq genomic : EntrezAC_000046 AC_000135 NC_000003 NG_007149 NT_005612 NW_001838884 NW_921807
    Consensus coding sequences : CCDS NCBIBCL6
    Cluster EST : UnigeneHs.478588 [ SRS ] Hs.478588 [ NCBI ]
    Alternative Splicing : Fast-db (Paris)15492
    Protein : pattern, domain, 3D structure
    Protein : UniProt/SwissProtP41182 (SRS) P41182 (Expasy) P41182 (Uniprot)
    With graphics : InterProP41182
    Splice isoforms : VarSplice FASTAP41182(VarSplice FASTA)
    Domaine pattern : Prosite (SRS)BTB (PS50097)    ZINC_FINGER_C2H2_1 (PS00028)    ZINC_FINGER_C2H2_2 (PS50157)   
    Domain pattern : Prosite (Expaxy)BTB (PS50097)    ZINC_FINGER_C2H2_1 (PS00028)    ZINC_FINGER_C2H2_2 (PS50157)   
    Domains : Interpro (SRS)BTB/POZ-like    BTB/POZ_fold    BTB_POZ    Znf_C2H2    Znf_C2H2-like    Znf_C2H2/integrase_DNA-bd   
    Domains : Interpro (EBI)BTB/POZ-like    BTB/POZ_fold    BTB_POZ    Znf_C2H2    Znf_C2H2-like    Znf_C2H2/integrase_DNA-bd   
    Related proteins : CluSTrP41182
    Domain families : Pfam SRSBTB (PF00651)    zf-C2H2 (PF00096)   
    Domain families : Pfam SangerBTB (PF00651)    zf-C2H2 (PF00096)   
    Domain families : Pfam NCBIpfam00651    pfam00096   
    Domain families : Smart EMBLBTB (SM00225)  ZnF_C2H2 (SM00355)  
    Blocks (Seattle)P41182
    Crystal structure of protein : PDB SRS1R28    1R29    1R2B    2EN2    2EOS    2YRM    3BIM    3E4U   
    Crystal structure of protein : PDBSum1R28    1R29    1R2B    2EN2    2EOS    2YRM    3BIM    3E4U   
    Crystal structure of protein : IMB1R28    1R29    1R2B    2EN2    2EOS    2YRM    3BIM    3E4U   
    Crystal structure of protein : PDB RSDB1R28    1R29    1R2B    2EN2    2EOS    2YRM    3BIM    3E4U   
    Human Protein AtlasENSG00000113916
    HPRD00180
    Protein Interaction databases
    DIP (DOE-UCLA)P41182
    IntAct (EBI)P41182
    FunCoupENSG00000113916
    Polymorphism : SNP, mutations, diseases
    Single Nucleotide Polymorphism (SNP) : dbSNP NCBIBCL6
    SNP : GeneSNP UtahBCL6
    SNP : HGBaseBCL6
    Genetic variants : HAPMAPBCL6
    Cancer Gene: CensusBCL6 
    Somatic Mutations in Cancer : COSMICBCL6 
    Translocation Breakpoints in Cancer : TICdbBCL6 
    Mutations and Diseases : HGMDBCL6
    Hereditary diseases : OMIM109565   
    Hereditary diseases : GENETests109565   
    Diseases : Genetic AssociationBCL6
    General knowledge
    Homologs : HomoloGeneBCL6
    Homology/Alignments : Family Browser UCSCBCL6
    Phylogenetic Trees/Animal Genes : TreeFamBCL6
    Chemical/Protein Interactions : CTD604
    Keywords Ontology : AmiGOprotein import into nucleus, translocation  negative regulation of transcription from RNA polymerase II promoter  cell morphogenesis  negative regulation of cell-matrix adhesion  regulation of germinal center formation  negative regulation of T-helper 2 type immune response  negative regulation of B cell apoptosis  chromatin binding  transcription factor activity  protein binding  intracellular  nucleus  replication fork  response to DNA damage stimulus  spermatogenesis  protein localization  zinc ion binding  negative regulation of cell proliferation  transcription repressor activity  transcription repressor activity  transcription repressor activity  actin cytoskeleton organization  B cell differentiation  negative regulation of cell growth  positive regulation of B cell proliferation  chromatin DNA binding  regulation of Rho GTPase activity  negative regulation of mast cell cytokine production  negative regulation of Rho protein signal transduction  positive regulation of apoptosis  negative regulation of apoptosis  regulation of memory T cell differentiation  sequence-specific DNA binding  regulation of transcription  negative regulation of cell differentiation  negative regulation of T-helper 2 cell differentiation  negative regulation of S phase of mitotic cell cycle  metal ion binding  negative regulation of isotype switching to IgE isotypes  erythrocyte development  regulation of inflammatory response  regulation of immune response  positive regulation of cellular component movement  
    Keywords Ontology : EGO-EBIprotein import into nucleus, translocation  negative regulation of transcription from RNA polymerase II promoter  cell morphogenesis  negative regulation of cell-matrix adhesion  regulation of germinal center formation  negative regulation of T-helper 2 type immune response  negative regulation of B cell apoptosis  chromatin binding  transcription factor activity  protein binding  intracellular  nucleus  replication fork  response to DNA damage stimulus  spermatogenesis  protein localization  zinc ion binding  negative regulation of cell proliferation  transcription repressor activity  transcription repressor activity  transcription repressor activity  actin cytoskeleton organization  B cell differentiation  negative regulation of cell growth  positive regulation of B cell proliferation  chromatin DNA binding  regulation of Rho GTPase activity  negative regulation of mast cell cytokine production  negative regulation of Rho protein signal transduction  positive regulation of apoptosis  negative regulation of apoptosis  regulation of memory T cell differentiation  sequence-specific DNA binding  regulation of transcription  negative regulation of cell differentiation  negative regulation of T-helper 2 cell differentiation  negative regulation of S phase of mitotic cell cycle  metal ion binding  negative regulation of isotype switching to IgE isotypes  erythrocyte development  regulation of inflammatory response  regulation of immune response  positive regulation of cellular component movement  
    Pathways : BIOCARTA
    Pathways : KEGG
    Other databases
    Probes
    Probes : ImagenesBCL6 Related clones (RZPD - Berlin)
    Literature
    PubMed166 Pubmed reference(s) in Entrez
    PubGeneBCL6

    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 articlesautomatic search in PubMed
    Last year publicationsautomatic search in PubMed

    Search in all EBI   NCBI

    Contributor(s)

    Written09-1998Jean-Pierre Kerkaert
    Unité 124 INSERM, Institut de Recherches sur le Cancer, Place de Verdun, 59045 LILLE cedex, FRANCE
    Updated02-2007Stevan Knezevich
    BC Cancer Research Centre (BCCRC), Vancouver, British Columbia, Canada.

    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. February 2007 .
    URL : http://AtlasGeneticsOncology.org/Genes/BCL6ID20.html

    © Atlas of Genetics and Cytogenetics in Oncology and Haematology
    indexed on : Thu Jul 15 14:51:19 CEST 2010
    Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

    For comments and suggestions or contributions, please contact us

    jlhuret@AtlasGeneticsOncology.org.