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t(14;22)(q32;q11) IGH/IGL

Written2008-06Hege Vangstein Aamot, Jan Delabie
Section for Cancer Cytogenetics, Department of Medical Genetics (HVA); Department of Pathology, Rikshospitalet University Hospital, Montebello, 0310 Oslo, Norway (JD)

(Note : for Links provided by Atlas : click)

Identity

ICD-Topo C420,C421,C424 BLOOD, BONE MARROW, & HEMATOPOIETIC SYS
ICD-Morpho 9861/3 AML with mutated NPM1; AML with mutated CEBPA; Acute myeloid leukaemia, NOS
Atlas_Id 1076
 
  t(14;22)(q32;q11) shown in ideograms and in G-banding. Both normal and rearranged chromosomes are shown. Arrows indicate the positions of the breakpoints - Courtesy Hege Vangstein Aamot, Jan Delabie; bottom row: Courtesy H. Norback, Eric B. Johnson, Sara Morrison-Delap UW Cytogenetic Services .

Clinics and Pathology

Disease Lymphoid malignancies
Note t(14;22)(q32;q11) analysed by G-banding has been reported in ALL, CLL/SLL, HCL, AML, NHL. Involvement of the genes IGH at 14q32 and IGL at 22q11 has been detected in one SLL and one DLBCL with t(14;22)(q32;q11).
Phenotype / cell stem origin
  • Small lymphocytic lymphoma (SLL): CD20+, CD23+, CD5+, CD10-, cyclinD1-
  • Diffuse large B cell lymphoma (DLBCL): CD20+, BCL6+, CD10-, BCL2+
  • Clinics
  • SLL: Cervical lymphadenopathy
  • DLBCL: Generalized lymphadenopathy, night sweats, weight loss
  • Pathology
  • SLL: The lymph node showed diffuse infiltration with small lymphocytic cells with typical coarse clumped nuclear chromatin. Proliferation centers with paraimmunoblasts were present.
  • DLBCL: Diffuse proliferation of large atypical lymphoid cells
  • Cytogenetics

    Cytogenetics Morphological The t(14;22)(q32;q11) was seen as the sole rearrangement in the SLL case. In the DLBCL case, there were several additional rearrangements. The complete karyotype of the latter was 52,XY,+Y,+der(3)t(3;9)(p11;p21),del(3)(q21),+7,+9,der(9)t(3;9)(q21;p21)x2,t(14;22)(q32;q11),der(15)t(1;15)(q21;p11),del(16)(p13),i(17)(q10),+18,+mar. The apparently identical translocation by G-banding has been seen in chronic myeloid leukaemia as well. However, this has been shown to be a three-way variant translocation of the classical t(9;22)(q34;q11) involving the genes ABL (9q34) and BCR (22q11).
    Cytogenetics Molecular Fluorescence in situ hybridization (FISH) analysis with locus-specific probes covering parts of IGH (PAC 998D24) and IGL (PAC 1019H10) showed fusion signals between the two probes. In the DLBCL case (figure to the left), two fusion signals were seen, indicating a reciprocal translocation between the two genes. In the SLL case (figure to the right), however, only the IGL probe was split and moved close to the IGH probe. The IGH probe remained seemingly intact on the der(14). To pinpoint more exact the breakpoint in IGL, three segments of the IGL probe were made using Long Range PCR. These segments were used as probes in further FISH analyses. In the SLL case, a split signal in the first segment probe was seen, locating the breakpoint between 12600bp and 37000bp from the centromeric end of the IGL probe. In the DLBCL case, a split signal in all the three segments was seen. One explanation might be that the IGL was duplicated and that one copy was moved to der(14). Another explanation might be that there was more than one breakpoint within IGL.
     
      The left image shows FISH analysis on an interphase nuclei from the SLL case and the right image shows FISH analysis on a metaphase spread from the DLBCL case. The arrows point to the fusion signals of the IGH (PAC 988D24, 14q32) and IGL (PAC 1019H10, 22q11) probes. In the DLBCL case, a reciprocal translocation was seen where both IGH and IGL probes were split and juxtaposed. In the SLL case, however, only the IGL probe was split and moved to der(14).

    Genes involved and Proteins

    Gene Name IGH
    Location 14q32
    Dna / Rna IGH is composed of variable (IGHV), diversity (IGHD), joining (IGHJ), and constant (IGHC) segments.
    Protein IGH encodes the immunoglobulin heavy chains.
    Gene Name IGL
    Location 22q11
    Dna / Rna IGL is composed of variable (IGLV), joining (IGLV), and constant segments (IGLC).
    Protein IGL encodes the immunoglobulin lambda chains.

    Result of the chromosomal anomaly

    Fusion Protein
    Note Rearrangements of the three immunoglobulin genes IGK (2p12), IGH (14q32), and IGL (22q11) are often seen, especially in NHL, but it is uncommon that these genes are recombined with each other. None of these genes are known oncogenes, so how juxtaposition or fusion of the IGH and IGL in the t(14;22)(q32;q11) might act pathogenetically is completely unknown. In the SLL case, a gene dose effect of the IGL may be important if there really are two copies of the gene. However, how this may contribute to lymphoma development is not understood. In the DLBCL case, only the IGL probe was split and moved to der(14). There is a possibility that there is another, nearby gene that is involved and not the IGH. On the other hand, the breakpoint may be distal to our IGH probe and still be within the IGH gene.
      

    To be noted

    Additional cases are needed to delineate the epidemiology of this rare entity:
    you are welcome to submit a paper to our new Case Report section.

    Bibliography

    t(14;22)(q32;q11) in non-Hodgkin lymphoma and myeloid leukaemia: molecular cytogenetic investigations.
    Aamot HV, Bjornslett M, Delabie J, Heim S.
    Br J Haematol. 2005 Sep;130(6):845-51.
    PMID 16156854
     
    World Health Organization Classification of Tumours. Pathology and genetics of tumours of haematopoietic and lymphoid tissues.
    Jaffe ES, Harris NL, Stein H, Vardiman JW (eds.).
    IARC Press: Lyon 2001.
     

    Citation

    This paper should be referenced as such :
    Aamot, HV ; Delabie, J
    t(14;22)(q32;q11)
    Atlas Genet Cytogenet Oncol Haematol. 2009;13(6):439-440.
    Free journal version : [ pdf ]   [ DOI ]
    On line version : http://AtlasGeneticsOncology.org/Anomalies/t1422q32q11ID1076.html


    Translocations implicated (Data extracted from papers in the Atlas)

     t(14;22)(q32;q11) IGH/IGL

    External links

    IGH (14q32.33) IGL (22q11.22)

    Mitelman databaset(14;22)(q32;q11) [Case List]    t(14;22)(q32;q11) [Association List] Mitelman database (CGAP - NCBI)
    arrayMapTopo ( C42) Morph ( 9861/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
     
    Mitelman databaseIGH/IGL [MCList]  IGH (14q32.33) IGL (22q11.22)
     
    Disease databaset(14;22)(q32;q11) IGH/IGL
    REVIEW articlesautomatic search in PubMed
    Last year articlesautomatic search in PubMed
    All articlesautomatic search in PubMed


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