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

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

t(2;18)(p11;q21)

t(18;22)(q21;q11)

Identity

Note the 3 translocations are variants of each other, and they share the same clinical significance

Left, from top to bottom: t(2;18)(p11;q21), t(14;18)(q32;q21), t(18;22)(q21;q11), G- banding - Courtesy Jean-Luc Lai and Alain Vanderhaegen; and, right: t(14;18)(q32;q21), R- banding - Editor

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)

External links

Other database t(14;18)(q32;q21) (IgH/BCL2) Mitelman database (CGAP - NCBI)

Other database t(14;18)(q32;q21) (IgH/BCL2) CancerChromosomes (NCBI)

Other database t(2;18)(p11;q21) Mitelman database (CGAP - NCBI)

Other database t(2;18)(p11;q21) CancerChromosomes (NCBI)

Other database t(18;22)(q21;q11) Mitelman database (CGAP - NCBI)

Other database t(18;22)(q21;q11) CancerChromosomes (NCBI)

Other database BCL2/IGH translocation (18/14) (Bari)

Probe BCL2 (18q21) in normal cells (Bari)

Probe IGH (14q32.33) in normal cells (Bari)

Other database	t(14;18)(q32;q21) (IgH/BCL2)	Mitelman database (CGAP - NCBI)
Other database	t(14;18)(q32;q21) (IgH/BCL2)	CancerChromosomes (NCBI)
Other database	t(2;18)(p11;q21)	Mitelman database (CGAP - NCBI)
Other database	t(2;18)(p11;q21)	CancerChromosomes (NCBI)
Other database	t(18;22)(q21;q11)	Mitelman database (CGAP - NCBI)
Other database	t(18;22)(q21;q11)	CancerChromosomes (NCBI)
Other database	BCL2/IGH translocation (18/14) (Bari)
Probe	BCL2 (18q21) in normal cells (Bari)
Probe	IGH (14q32.33) in normal cells (Bari)

Bibliography

Cytogenetic evolution patterns in non-Hodgkin's lymphoma.

Johansson B, Mertens F, Mitelman F

Blood. 1995 ; 86 (10) : 3905-3914.

PMID 7579360

Non-Hodgkin's lymphoma.

Maloney DG

Current opinion in hematology. 1995 ; 2 (4) : 255-261.

PMID 9372005

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 mechanisms in the pathogenesis and progression of follicular lymphoma.

Knutsen T

Cancer surveys. 1997 ; 30 : 163-192.

PMID 9547992

Contributor(s)

Written 05-1998 Jean-Loup Huret

Citation

This paper should be referenced as such :
Huret JL . t(14;18)(q32;q21) (IgH/BCL2); t(2;18)(p11;q21); t(18;22)(q21;q11). Atlas Genet Cytogenet Oncol Haematol. May 1998 .
URL : http://AtlasGeneticsOncology.org/Genes/t1418ID2006.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Wed Sep 24 21:07:33 2008

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For comments and suggestions or contributions, please contact us

j.l.huret@chu-poitiers.fr.

Note	the 3 translocations are variants of each other, and they share the same clinical significance


	Left, from top to bottom: t(2;18)(p11;q21), t(14;18)(q32;q21), t(18;22)(q21;q11), G- banding - Courtesy Jean-Luc Lai and Alain Vanderhaegen; and, right: t(14;18)(q32;q21), R- banding - Editor

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)



	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

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

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

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)