t(3;14)(q27;q32) IGH/BCL6
t(2;3)(p12;q27) IGK/BCL6
t(3;22)(q27;q11) IGL/BCL6

1998-04-01   Christian Bastard  

1.Department of Hematology, Centre Henri Becquerel, Rouen, France

Clinics and Pathology

Disease

NHL; mainly diffuse large cell lymphoma (DLCL); high gradelymphoma; rare cases with low grade/follicular lymphoma; in those cases, 3qrearrangements can be isolated or associated with a t(14;18) translocation

Phenotype stem cell origin

B-cell

Epidemiology

3q27 rearrangements present in 25 to 30 % of DLCL; about 10 %of follicular lymphoma

Clinics

mainly adult aggressive lymphoma

Treatment

intensive chemotherapy

Prognosis

controversial

Cytogenetics

Cytogenetics morphological

t(2;3) and t(3;22) are easily identified; t(3 ;14) istelomeric and difficult to see, especially when using G banding

Cytogenetics molecular

some cosmid and YAC probes have been developed

Additional anomalies

very frequent, as usual in NHL, involving chromosome1, del(6q), 10q, 11q, 12q, 13q, 17p arms

Variants

large number of recurring defects involving the 3q27 region:t(3;4)(q27;p13), t(3;6)(q27;p22), t(3;7)(q27;p13),t(3;8)(q27;q24), t(3;11)(q27;q23),t(3;13)(q27;q14), t(3;15)(q27;q22), t(3;17)(q27;q11).

Genes Involved and Proteins

Note
BCL 6 (see below) with various partners: immunoglobulin genes IgH(mainly Sμ region) in 14q32, IgK in 2p12, and IgL in22q11; (for variant translocations, partners are: RHOH in thet(3;4), histone H1F1 in the t(3;6), OBF1 in the t(3;11),LCP1 in the t(3;13); in these cases, the first non-coding exon ofthe partner gene fuses with the second exon of BCL6, resulting in thederegulated expression of a chimerical transcript and the production of anormal BCL6 protein)
Gene name
BCL6 (B-Cell Lymphoma 6)
Location
3q27.3
Dna rna description
10 exons; alternative splicing of exons 1 (1a and 1b),without modification of the open reading frame
Protein description
transcription factor; belongs to the Krüppel family,with a N-term BTB/POZ domain and 6 zinc fingers; transcription repressor.

Result of the Chromosomal Anomaly

Description

no fusion protein, but promoter exchange; the immunoglobulingene promoter controls the expression of the BCL6 gene.

Oncogenesis

deregulated protein expression; alternative deregulationmechanisms: deletion of regulating sequences, mutations.

Highly cited references

Pubmed IDYearTitleCitations
259918192015Genome-Wide Analysis Uncovers Novel Recurrent Alterations in Primary Central Nervous System Lymphomas.71
85570401995Chromosomal translocations cause deregulated BCL6 expression by promoter substitution in B cell lymphoma.59
237757152013A capture-sequencing strategy identifies IRF8, EBF1, and APRIL as novel IGH fusion partners in B-cell lymphoma.26
186451922008Del(6)(q22) and BCL6 rearrangements in primary CNS lymphoma are indicators of an aggressive clinical course.26
208540732010Primary central nervous system lymphoma: a clinicopathological study of 75 cases.16
301714532018Characterization of genomic alterations in primary central nervous system lymphomas.10
208307192011BCL6 gene rearrangement and protein expression are associated with large cell presentation of extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue.9
160493072005Molecular cytogenetic analyses of immunoglobulin loci in nodular lymphocyte predominant Hodgkin's lymphoma reveal a recurrent IGH-BCL6 juxtaposition.8
255962562015Cyclin D1-positive diffuse large B-cell lymphoma with IGH-CCND1 translocation and BCL6 rearrangement: a report of two cases.4
231359542013Chromosome abnormalities in diffuse large B-cell lymphomas: analysis of 231 Chinese patients.2
228678982012IGH@/BCL6 rearrangement on the der(3)t(3;14)(q27;q32) in primary mediastinal large B-cell lymphoma.2

Article Bibliography

Pubmed IDLast YearTitleAuthors
85063751993Identification of the gene associated with the recurring chromosomal translocations t(3;14)(q27;q32) and t(3;22)(q27;q11) in B-cell lymphomas.Baron BW et al
81673311994LAZ3 rearrangements in non-Hodgkin's lymphoma: correlation with histology, immunophenotype, karyotype, and clinical outcome in 217 patients.Bastard C et al
15867041992Translocations involving band 3q27 and Ig gene regions in non-Hodgkin's lymphoma.Bastard C et al
75096221993Cloning of a breakpoint cluster region at band 3q27 involved in human non-Hodgkin's lymphoma.Deweindt C et al
82204271993LAZ3, a novel zinc-finger encoding gene, is disrupted by recurring chromosome 3q27 translocations in human lymphomas.Kerckaert JP et al
82747401994Gene involved in the 3q27 translocation associated with B-cell lymphoma, BCL5, encodes a Krüppel-like zinc-finger protein.Miki T et al
82082681994Rearrangement of the bcl-6 gene as a prognostic marker in diffuse large-cell lymphoma.Offit K et al
82355961993Alterations of a zinc finger-encoding gene, BCL-6, in diffuse large-cell lymphoma.Ye BH et al
85044121993Cloning of bcl-6, the locus involved in chromosome translocations affecting band 3q27 in B-cell lymphoma.Ye BH et al

Summary

Fusion gene

IGL/BCL6 IGL (22q11.22) BCL6 (3q27.3) M t(3;22)(q27;q11)

Note

the three translocations are variant of each other, share identicalfeatures, and represent translocations of the same proto-oncogene intovarious immunoglobulin loci.
Atlas Image
t(2;3)(p12;q27) G- banding (above) - Courtesy Jean-Luc Lai and Alain Vanderhaegen; t(3;14)(q27;q32) G-banding (middle) and t(3;22)(q27;q11) G-banding (below) - Courtesy Diane H. Norback, Eric B. Johnson, and Sara Morrison-Delap, UW Cytogenetic Services

Citation

Christian Bastard

t(3;14)(q27;q32) IGH/BCL6
t(2;3)(p12;q27) IGK/BCL6
t(3;22)(q27;q11) IGL/BCL6

Atlas Genet Cytogenet Oncol Haematol. 1998-04-01

Online version: http://atlasgeneticsoncology.org/haematological/2004/t(3;22)(q27;q11)