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t(14;18)(q32;q21) IGH/BCL2

t(2;18)(p11;q21) IGK/BCL2

t(18;22)(q21;q11) IGL/BCL2

Written1998-05Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

(Note : for Links provided by Atlas : click)

Identity

ICD-Topo C420,C421,C424 BLOOD, BONE MARROW, & HEMATOPOIETIC SYS
ICD-Morpho 9811/3 B lymphoblastic leukaemia/lymphoma, NOS
Atlas_Id 2006
Note the 3 translocations are variants of each other, and they share the same clinical significance
 
  Inset top right: t(14;18)(q32;q21) FISH - Courtesy Hossein Mossafa; First row: t(2;18)(p11;q21), G- banding - Courtesy Jean-Luc Lai and Alain Vanderhaegent. Second row: (14;18)(q32;q21), G- banding - Courtesy Jean-Luc Lai and Alain Vanderhaegen (left), and H. Norback, Eric B. Johnson, Sara Morrison-Delap UW Cytogenetic Services (centre); R- banding - Jean Loup Huret (top), and Courtesy Hossein Mossafa (bottom). Third row: t(18;22)(q21;q11), G- banding - Courtesy Jean-Luc Lai and Alain Vanderhaegen (left) ; and, H. Norback, Eric B. Johnson, Sara Morrison-Delap UW Cytogenetic Services (centre).

Clinics and Pathology

Disease B- cell NHL mainly; may (rarely) be found in ALL or in chronic lymphoproliferative diseases
Phenotype / cell stem origin B lymphocyte; the translocation occurs at the pre B cell stage
Epidemiology found in 80 to 90 % of follicular lymphomas, 30% of diffuse large cell lymphomas (sometimes with prior follicular type), rarely in other lymphoproliferative disorders
Prognosis small cleaved cell follicular lymphomas have a slow evolutivity and a median survival of 10 yrs or more; large cell lymphomas have a worse prognosis; the t(14;18) may have little or no prognostic significance, which would be in accordance with its 'oncogenic' role (see below)

Cytogenetics

 
  BAC248E24 (BCL2, 18q21, green) cohybridized with PAC PAC 998D24 (14q32.3, red, centromeric to the breakpoint) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics
Cytogenetics Morphological the t(14;18) is well recognized with G-banding, may be overlocked with R-banding; the t(2;18)( p11;q21) and the t(18;22(q21;q11) are rare variants
Additional anomalies found in 90% of cases; complex karyotypes are frequent; by decreasing order, +7, del(6q), +12, + X, + 18, +5, +8, + der(18), + 21 are found in 25 to 10% of cases; +X and del(6q) more frequently in low grade, +7,+8, +der(18), and also the addition of a t(8;14)(q24;q32) more often in high grade NHL

Genes involved and Proteins

Gene Name IGH
Location 14q32
Dna / Rna IGH is composed of IGHV genes, IGHD segments, IGHJ segments, and IGHC genes.
Protein IGH encodes the immunoglobulin heavy chains. They result from the DNA rearrangement (with deletion of the intermediary DNA) of IGHV, IGHD and IGHJ; an additional DNA rearrangement (switch) with constant genes IGHM --> IGHG, IGHA and IGHE can occur.
Gene Name BCL2
Location 18q21
Dna / Rna 3 exons; 2 alternative transcripts (a and b)
Protein member of the BCL2 family (with BAX, BCLX,...); contains dimerization domains (BH) and NH domains; BCL2a contains a hydrophobic tail for membrane anchorage; inhibits cell death process through heterodimerization

Result of the chromosomal anomaly

Hybrid gene
Description 5' BCL2 translocated on chromosome 14 near JH (junctions genes of IgH) and C in 3'; the breakpoint in BCL2 is either in the 3' untranslated region of exon 3 (major breakpoint region (MBR) in 70% of cases) or more distal, in 3' of exon 3 (minor cluster region (MCR) in the remaining 30%); illegitimate recombination
  
Fusion Protein
Description no fusion protein, but promoter exchange; the immunoglobulin gene enhancer stimulates the expression of BCL2
Oncogenesis as BCL2 is an apoptosis inhibitor, cell death is delayed, and there is cell accumulation more than real transformation (clones of long living B-cells with t(14;18) may even be seen in the normal population, and with frequency increasing with age)
  

Bibliography

Cytogenetics of lymphomas: a brief review of its theoretical and practical significance.
Donner LR
Cancer genetics and cytogenetics. 1997 ; 94 (1) : 20-26.
PMID 9078287
 
Cytogenetic evolution patterns in non-Hodgkin's lymphoma.
Johansson B, Mertens F, Mitelman F
Blood. 1995 ; 86 (10) : 3905-3914.
PMID 7579360
 
Cytogenetic mechanisms in the pathogenesis and progression of follicular lymphoma.
Knutsen T
Cancer surveys. 1997 ; 30 : 163-192.
PMID 9547992
 
Non-Hodgkin's lymphoma.
Maloney DG
Current opinion in hematology. 1995 ; 2 (4) : 255-261.
PMID 9372005
 

Citation

This paper should be referenced as such :
Huret, JL
t(14;18)(q32;q21) - t(2;18)(p11;q21) - t(18;22)(q21;q11)
Atlas Genet Cytogenet Oncol Haematol. 1998;2(4):134-136.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Anomalies/t1418ID2006.html


Other genes implicated (Data extracted from papers in the Atlas) [ 4 ]

Genes BACH2 BCL2 FCGR2B IGH

Translocations implicated (Data extracted from papers in the Atlas)

 t(14;18)(q32;q21) IGH/BCL2
 t(18;22)(q21;q11) IGL/BCL2
 t(2;18)(p11;q21) IGK/BCL2

External links

IGK (14q32.33) BCL2 (18q21.33)

Mitelman databaset(14;18)(q32;q21) [Case List]    t(14;18)(q32;q21) [Association List] Mitelman database (CGAP - NCBI)
Mitelman databaset(18;22)(q21;q11) [Case List]    t(18;22)(q21;q11) [Association List] Mitelman database (CGAP - NCBI)
Mitelman databaset(2;18)(p11;q21) [Case List]    t(2;18)(p11;q21) [Association List] Mitelman database (CGAP - NCBI)
arrayMapTopo ( C42) Morph ( 9811/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
 
Mitelman databaseIGK/BCL2 [MCList]  IGK (14q32.33) BCL2 (18q21.33)
 
Other databaseBCL2/IGH translocation (18/14) (Bari)
Disease databaset(14;18)(q32;q21) IGH/BCL2
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed


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