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

1998-05-01   Jean-Loup Huret 

1.Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

Clinics and Pathology

Disease

B- cell NHL mainly; may (rarely) be found in ALL or in chronic lymphoproliferative diseases

Phenotype stem cell 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

Atlas Image
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 (Immunoglobulin Heavy)
Location
14q32.33
Dna rna description
IGH is composed of IGHV genes, IGHD segments, IGHJ segments, and IGHC genes.
Protein description
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 (B-cell leukemia/lymphoma 2)
Location
18q21.33
Dna rna description
3 exons; 2 alternative transcripts (a and b)
Protein description
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

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 recombinationno 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

Pubmed IDLast YearTitleAuthors
90782871997Cytogenetics of lymphomas: a brief review of its theoretical and practical significance.Donner LR et al
75793601995Cytogenetic evolution patterns in non-Hodgkin's lymphoma.Johansson B et al
95479921997Cytogenetic mechanisms in the pathogenesis and progression of follicular lymphoma.Knutsen T et al
93720051995Non-Hodgkin's lymphoma.Maloney DG et al

Summary

Fusion gene

IGK/BCL2 IGK (14q32.33) BCL2 (18q21.33) M t(2;18)(p11;q21)

Note

the 3 translocations are variants of each other, and they share the same clinical significance
Atlas Image
t(14;18)(q32;q21) IGH/BCL2 , t(2;18)(p11;q21), t(18;22)(q21;q11), BCL2 Top: 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); - Courtesy Adriana Zamecnikova (bottom tree); R- banding - Jean Loup Huret (top), and Courtesy Hossein Mossafa (bottom). FISH - Courtesy Hossein Mossafa (center); Hybridization with Vysis LSI IGH/BCL dual color probe (Abbott Molecular, US) showing fused yellow signals on der(14) and der(18) chromosomes - Courtesy Adriana Zamecnikova. Middle: t(2;18)(p11;q21), G- banding - Courtesy Jean-Luc Lai and Alain Vanderhaegent. Bottom: 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). BCL2: BAC248E24 (BCL2, 18q21, green) cohybridized with PAC PAC 998D24 (14q32.3, red, centromeric to the breakpoint) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics

Citation

Jean-Loup Huret

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

Atlas Genet Cytogenet Oncol Haematol. 1998-05-01

Online version: http://atlasgeneticsoncology.org/haematological/2006/t(14;18)(q32;q21)

External Links