t(2;19)(p12;q13.3) IGK/BCL3

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Written2001-08Peter Meeus, Lucienne Michaux
Centrum voor Menselijke Erfelijkheid, UZ Gasthuisberg, Herestraat 49, 3000 Leuven, Belgie
Updated2008-06Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers; CHU Poitiers Hospital, F-86021 Poitiers, France

(Note : for Links provided by Atlas : click)

1. Identity

ICD-Topo C420,C421,C424 BLOOD, BONE MARROW, & HEMATOPOIETIC SYS
Atlas_Id 2050
Note The t(14;19)(q32.3;q13.3) -as well as the variants t(2;19) and t(19;22)- is a recurrent translocation found in patients with chronic B-cell lymphoproliferative disorders.
This abnormality is cytogenetically identical but molecularly distinct from the t(14;19)(q32;q13) with IGH and CEBPA (or CEBPG) involvements, seen in acute B-cell lymphoblastic leukaemia.
 
  t(14;19)(q32;q13) G-banding Left: - Courtesy Jean-Luc Lai (top) and Diane H Norback, Eric B Johnson, and Sara Morrison-Delap, http://www.slh.wisc.edu/cytogenetics (middle and bottom); right: top: ideograms, bottom middle two: G and R-bandings - Courtesy Peter Meus; R-banding (right) : Coutesy Chrystèle Bilhou-Nabera and Nasséra Abermil.

2. Clinics and Pathology

Disease Chronic lymphocytic leukemia/small lymphocytic lymphoma (B-CLL/SLL); most are the atypical form (at times reported as variant CLL, or transformed CLL), because of an atypical morphology and phenotype (Michaux et al., 1996; Michaux et al., 1997), but also for the presence of lymphocytosis (Soma et al., 2006), the frequency of lymphadenopathy (Huh et al., 2007), young age (median 50-60 years), male predominence (about 2M/1F), and an aggressive course of the disease (Michaux et al., 1997).
Other diseases: marginal zone lymphoma (MZL), splenic marginal zone lymphoma (SMZL), diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma, low grade B-cell non Hodgkin lymphoma (NHL) not otherwise specified, aggressive B-cell NHL, and even one case of biphenotypic (B/M) acute leukemia.
A recent study reascertained and split the entity into the following subgroups herein below described; the accuracy of this proposal remains to be confirmed by further studies, inasmuch as there is a real problem of classification of t(14;19)(q32;q13) in chronic B-cell lymphoproliferative disorders, as has been pointed out (Soma et al., 2006; Huh et al., 2007):
"7q rearrangements cluster": 15% of cases: diagnosis of MZL/SMZL or aggressive B-cell NHL mostly. Medium complexity of the karyotype. IgVH mutated. Aggressive diseases. Median age 65 (49-85).
"Deletion 17p cluster": 10% of cases: diagnosis of CLL frequent. Complex karyotypes. IgVH mutated. Median age 54.
"1q rearrangements, deletions 6q and 13q cluster": 30% of cases: diagnosis of DLBCL or MZL and MZL in transformation, less often, CLL. Complex karyotypes. IgVH mutated. Aggressive diseases. Median age 65 (27-92).
"Trisomy 12 cluster": 45% of cases: diagnosis of CLL in most cases, low complexity of the karyotype, IgVH mutation rate low. This is the only cluster with an unequal sex ratio: 14M/4F; median age 65 (35-95).
Phenotype / cell stem origin Chronic B-cell lymphoproliferation
Epidemiology 103 published cases (40 reviewed in Soma et al., 2006; 7 cases in Huh et al., 2007; and 56 cases in Martin-Subero et al., 2007). Annual incidence 30/106. The t(14;19) occurs in less than 0.2 % of B-cell malignancies.
Clinics Often a slow evolutive disease.
Prognosis Highly variable according to the staging: from staging A: where the survival is not reduced compared to age matched population, to staging C: with a median survival of 2 yrs. t(14;19) is often associated with rapidly progressive disease, and overall prognosis is poor compared to the expected survival in chronic lymphocytic leukemia and low-grade B-cell lymphoma. The prognosis has to be reascertained according to new (or further) sub-classification of the the disease.

3. Cytogenetics

Cytogenetics Morphological The t(14;19)(q32.3;q13.2) is reciprocal and results in 14q+ and a 19q- derivative chromosomes.
Cytogenetics Molecular FISH is useful for identifying variant translocations.
Additional anomalies t(14;19) is rarely the sole cytogenetic aberration. Trisomy 12 is the most frequent associated abnormality, and is observed in 50% of cases. del(6q), del(7q), del(13q), del(17p) and additional 14q32 rearrangements can be found. Other chromosomes involved in structural aberrations are 1q, 3p, 3q, 6p, 7q, 11q, 12p.
Variants t(2;19)(p12;q13) IGK/BCL3 and t(19;22)(q13;q11) BCL3/IGL, variants of the t(14;19)(q32;q13) IGH/BCL3, have been described; they are found in the same proportions as for the variants of the t(8;14)(q24;q32).

4. Genes involved and Proteins

Gene NameIGH (Immunoglobulin Heavy)
Location 14q32.33
Note IgK or IgL can replace IgH (see above).
Gene NameBCL3 (B-cell CLL/lymphoma 3)
Location 19q13.32
Dna / Rna 9 exons, spanning 11.5 kb. BCL3 mRNA is expressed in a variety of tissues, particularly in spleen, liver and lung.
Protein
  • Encodes a protein which contains seven ankyrin repeats. Similar repeats are described in the structural protein ankyrin, as well as in proteins involved in cell cycle control and lineage determination (SW14, SW16, lin2).
  • BCL3 is a member of the IkappaB family, whose proteins regulate the NFkappaB family of transcription factors. NFkappaB plays a major role in B-cell development.

    • 5. Result of the chromosomal anomaly

    Hybrid gene
    Description The breakpoint is located in the 5' untranslated region of the BCL3 gene. BCL3 is juxtaposed to the immunoglobulin heavy chain gene locus on chromosome 14 (often in the switch alpha region) in a "head-to-head" configuration.
      
    Fusion Protein
    Oncogenesis
  • No fusion protein. The translocation does not interrupt the transcriptional integrity of BCL3, but is associated with increased production of a BCL3 RNA of normal size. The immunoglobulin enhancer is not present on the same derivative chromosome as BCL3, suggesting other mechanisms for overexpression.
  • The genes affected by overexpression of BCL3 remain to be identified.
    •   

    6. Bibliography

    The t(14;19)(q32;q13)-positive small B-cell leukaemia: a clinicopathologic and cytogenetic study of seven cases.
    Huh YO, Abruzzo LV, Rassidakis GZ, Parry-Jones N, Schlette E, Brito-Bapabulle V, Matutes E, Wotherspoon A, Keating MJ, Medeiros LJ, Catovsky D.
    Br J Haematol. 2007 Jan;136(2):220-8.
    PMID 17129229
     
    A comprehensive genetic and histopathologic analysis identifies two subgroups of B-cell malignancies carrying a t(14;19)(q32;q13) or variant BCL3-translocation.
    Mart'n-Subero JI, Ibbotson R, Klapper W, Michaux L, Callet-Bauchu E, Berger F, Calasanz MJ, De Wolf-Peeters C, Dyer MJ, Felman P, Gardiner A, Gascoyne RD, Gesk S, Harder L, Horsman DE, Kneba M, Kuppers R, Majid A, Parry-Jones N, Ritgen M, Salido M, Sole F, Thiel G, Wacker HH, Oscier D, Wlodarska I, Siebert R.
    Leukemia. 2007 Jul;21(7):1532-44.
    PMID 17495977
     
    t(14;19)/BCL3 rearrangements in lymphoproliferative disorders: a review of 23 cases.
    Michaux L, Dierlamm J, Wlodarska I, Bours V, Van den Berghe H, Hagemeijer A.
    Cancer genetics and cytogenetics. 1997 ; 94 (1) : 36-43.
    PMID 9078289
     
    BCL3 rearrangement and t(14;19)(q32;q13) in lymphoproliferative disorders.
    Michaux L, Mecucci C, Stul M, Wlodarska I, Hernandez JM, Meeus P, Michaux JL, Scheiff JM, Noel H, Louwagie A, Criel A, Boogaerts M, Van Orshoven A, Cassiman JJ, Van Den Berghe H.
    Genes, chromosomes & cancer. 1996 ; 15 (1) : 38-47.
    PMID 8824724
     
    Splenic small B-cell lymphoma with IGH/BCL3 translocation.
    Soma LA, Gollin SM, Remstein ED, Ketterling RP, Flynn HC, Rajasenan KK, Swerdlow SH.
    Hum Pathol. 2006 Feb;37(2):218-30. (Review)
    PMID 16426923
     

    7. Citation

    This paper should be referenced as such :
    Huret, JL
    t(2;19)(p12;q13) IGK/BCL3 - t(14;19)(q32;q13) IGH/BCL3 - t(19;22)(q13;q11) BCL3/IGL
    Atlas Genet Cytogenet Oncol Haematol. 2009;13(6):441-443.
    Free journal version : [ pdf ]   [ DOI ]
    On line version : http://atlasgeneticsoncology.usal.es/classic/Anomalies/t1419ID2050.html
    History of this paper:
    Meeus, P ; Michaux, L. t(14;19)(q32;q13). Atlas Genet Cytogenet Oncol Haematol. 2001;5(4):292-293.
    http://documents.irevues.inist.fr/bitstream/handle/2042/37794/08-2001-t1419ID2050.pdf

    8. Translocations implicated (Data extracted from papers in the Atlas)

     t(14;19)(q32;q13.3) IGH/BCL3
     t(19;22)(q13.3;q11) BCL3/IGL
     t(2;19)(p12;q13.3) IGK/BCL3

    9. External links

    IGK (14q32.33) BCL3 (19q13.32)

    Mitelman databaset(14;19)(q32;q13.3) [Case List]    t(14;19)(q32;q13.3) [Transloc-MCList] IGH/BCL3 [Fusion-MCList]
    Mitelman databaset(19;22)(q13.3;q11) [Case List]    t(19;22)(q13.3;q11) [Transloc-MCList] BCL3/IGL [Fusion-MCList]
    Mitelman databaset(2;19)(p12;q13.3) [Case List]    t(2;19)(p12;q13.3) [Transloc-MCList] IGK/BCL3 [Fusion-MCList]
    arrayMap (UZH-SIB Zurich)[select an item]
     
    Mitelman databaseIGK/BCL3 [MCList]  IGK (14q32.33) BCL3 (19q13.32)
     
    REVIEW articlesautomatic search in PubMed
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    indexed on : Wed Nov 28 16:19:34 CET 2018

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