Download Leukaemia Section t(14;15)(q32;q11-13) Atlas of Genetics and Cytogenetics in Oncology and Haematology

Atlas of Genetics and Cytogenetics
in Oncology and Haematology
OPEN ACCESS JOURNAL AT INIST-CNRS
Leukaemia Section
Mini Review
t(14;15)(q32;q11-13)
Silvia Rasi, Gianluca Gaidano
Division of Hematology, Department of Clinical and Experimental Medicine & Center of Biotechnologies
for Applied Medical Research, Amedeo Avogadro University of Eastern Piedmont, Via Solaroli 17, 28100
Novara, Italy (SR, GG)
Published in Atlas Database: July 2008
Online updated version : http://AtlasGeneticsOncology.org/Anomalies/t1415q32q12ID1349.html
DOI: 10.4267/2042/44522
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2009 Atlas of Genetics and Cytogenetics in Oncology and Haematology
Clinics and pathology
Cytogenetics
Disease
Additional anomalies
Diffuse large B-cell lymphoma (DLBCL). DLBCL is a
molecularly heterogeneous type of aggressive
lymphoma, accounting for approximately 40% of all Bcell non-Hodgkin lymphomas (NHL) of the Western
world. Translocations involving the chromosomal
region 15q11-13 also have been identified in
nonlymphoid tumors.
DLBCL is a heterogeneous disease with respect to
karyotypic abnormalities. t(14;15)(q32;q11-13) is a rare
chromosomal translocation restricted to 4-5% DLBCL.
The most frequent cytogenetic abnormalities detected
in DLBCL involve BCL6 t(3;V)(q27;V), BCL2
t(14;18)(q32;q21), and myc t(8;14)(q24;q32), and
occur in 25%, 20% and 10% of DLBCL, respectively.
Phenotype/cell stem origin
Variants
B-cell.
The
chromosomal
translocation
t(14;15)(q32;q11-13) can activate BCL8 gene
expression in lymphoid tissues, whereas BCL8
expression is not normally found in hematopoietic
tissues.
In addition to IGHV gene translocation, other
translocations of the chromosomal region 15q11-13
involve additional chromosomal sites, including 22q11
(IGLV), 9p13, 1p32, 7p13, 12q24, and 15q22.
Genes involved and proteins
Epidemiology
IgH
Translocations affecting 15q11-q13 and various
chromosomal partners occur in about 3-4% of DLBCL.
Location
14q32
DNA/RNA
IgH gene is composed of V (variable), D (diversity), J
(joining), and C (constant) segments. During B cell
development, a recombination event at the DNA level
creates a rearranged IGHV-D-J gene.
Protein
Proteins encoded by the IgH gene are the
immunoglobulin heavy chains.
Clinics
At present, it is not not yet clear whether chromosomal
translocation t(14;15) identifies a homogeneous.
Pathology
Clinico-pathologic subtype of DLBCL.
Prognosis
The effect of BCL8 expression on the prognosis of
patients has yet to be investigated.
Atlas Genet Cytogenet Oncol Haematol. 2009; 13(7)
513
t(14;15)(q32;q11-13)
Rasi S, Gaidano G
BCL8
Fusion protein
Location
15q11-q13
DNA/RNA
3 exons. The 5' part of exon 1 and the 3' part of exon 3
are non coding. Two alternative transcripts: a major
transcript of 2.6 kb, and a less expressed transcript of
4.5 kb, due to differential polyadenylation.
Protein
100 amino acids, predicted molecular weight of 19
kDa; predicted: similar to protein neurobeachin
(Lysosomal trafficking regulator 2). Truncated
polypeptides with uncertain function are also produced.
Description
The chromosomal translocation does not lead to the
formation of a fusion protein.
Oncogenesis
t(14;15)(q32;q11-13) causes activation of the BCL8
proto-oncogene by deregulated expression of BCL8.
This chromosomal translocation may contribuite to
lymphomagenesis by alterated expression level of
BCL8.
References
Dyomin VG, Rao PH, Dalla-Favera R, Chaganti RS. BCL8, a
novel gene involved in translocations affecting band 15q11-13
in diffuse large-cell lymphoma. Proc Natl Acad Sci U S A. 1997
May 27;94(11):5728-32
Result of the chromosomal
anomaly
Macintyre E, Willerford D, Morris SW. Non-Hodgkin's
Lymphoma: Molecular Features of B Cell Lymphoma.
Hematology Am Soc Hematol Educ Program. 2000;:180-204
Hybrid gene
Description
The translocation t(14;15)(q32;q11-13) leaves the
coding region of BCL8 gene intact, and does not lead
to the formation of a hybrid gene. BCL8 is adjacent to
the chromosomal breakpoint, that is located upstream
of a rearranged VH segment. BCL8 is a part of a large
duplicated region within 15q11 containing several
pseudogenes, including orphan IGH copies of V and D
segments and it's possible that this V/D segments can
rearrange with D/J segments on chromosome 14.
Atlas Genet Cytogenet Oncol Haematol. 2009; 13(7)
Dyomin VG, Chaganti SR, Dyomina K, Palanisamy N, Murty
VV, Dalla-Favera R, Chaganti RS. BCL8 is a novel,
evolutionarily conserved human gene family encoding proteins
with presumptive protein kinase A anchoring function.
Genomics. 2002 Aug;80(2):158-65
Rossi D, Gaidano G. Molecular heterogeneity of diffuse large
B-cell lymphoma: implications for disease management and
prognosis. Hematology. 2002 Aug;7(4):239-52
This article should be referenced as such:
Rasi S, Gaidano G. t(14;15)(q32;q11-13). Atlas Genet
Cytogenet Oncol Haematol. 2009; 13(7):513-514.
514