Download Leukaemia Section t(14;18)(q32;q21) t(2;18)(p11;q21) t(18;22)(q21;q11)

Atlas of Genetics and Cytogenetics
in Oncology and Haematology
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Leukaemia Section
Mini Review
t(14;18)(q32;q21)
t(2;18)(p11;q21)
t(18;22)(q21;q11)
Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
Published in Atlas Database: May 1998
Online updated version: http://AtlasGeneticsOncology.org/Anomalies/t1418ID2006.html
DOI: 10.4267/2042/37459
This work is licensed under a Creative Commons Attribution-Non-commercial-No Derivative Works 2.0 France Licence.
© 1998 Atlas of Genetics and Cytogenetics in Oncology and Haematology
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.
Atlas Genet Cytogenet Oncol Haematol. 1998;2(4)
134
t(14;18)(q32;q21) ; t(2;18)(p11;q21) ; t(18;22)(q21;q11)
Huret JL
Additional anomalies
Clinics and pathology
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.
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).
Genes involved and Proteins
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.
Cytogenetics
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.
Results 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.
BAC248E24 (BCL2, 18q21, green) cohybridized with PAC
PAC 998D24 (14q32.3, red, centromeric to the breakpoint) Courtesy Mariano Rocchi, Resources for Molecular
Cytogenetics.
Fusion protein
Description
No fusion protein, but promoter exchange; the
immunoglobulin gene enhancer stimulates the
expression of BCL2.
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.
Atlas Genet Cytogenet Oncol Haematol. 1998;2(4)
135
t(14;18)(q32;q21) ; t(2;18)(p11;q21) ; t(18;22)(q21;q11)
Huret JL
Maloney DG. Non-Hodgkin's lymphoma. Curr Opin Hematol
1995 Jul;2(4):255-61. (Review).
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).
Donner LR. Cytogenetics of lymphomas: a brief review of its
theoretical and practical significance. Cancer Genet Cytogenet
1997 Mar;94(1):20-6. (Review).
Knutsen T. Cytogenetic mechanisms in the pathogenesis and
progression of follicular lymphoma. Cancer Surv 1997;30:16392. (Review).
References
This article should be referenced as such:
Johansson B, Mertens F, Mitelman F. Cytogenetic evolution
patterns in non-Hodgkin's lymphoma. Blood 1995 Nov
15;86(10):3905-14.
Atlas Genet Cytogenet Oncol Haematol. 1998;2(4)
Huret JL. t(14;18)(q32;q21); t(2;18)(p11;q21);
t(18;22)(q21;q11).
Atlas
Haematol.1998;2(4):134-136.
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