A comprehensive genetic and histopathologic analysis identifies two subgroups of B-cell malignancies carrying a t(14;19)(q32;q13) or variant BCL3-translocation.
The biologic and pathologic features of B-cell malignancies bearing a translocation t(14;19)(q32;q13) leading to a fusion of IGH and BCL3 are still poorly described. Herein we report the results of a comprehensive cytogenetic, fluorescence in situ hybridization (FISH), molecular and histopathological survey of a large series of B-cell malignancies with t(14;19) or variant translocations. A total of 56 B-cell malignancies with a FISH-proven BCL3 involvement were identified with the translocation partners being IGH (n=51), IGL (n=2), IGK (n=2) and a non-IG locus (n=1). Hierarchical clustering of chromosomal changes associated with the t(14;19) indicated the presence of two different groups of IG/BCL3-positive lymphatic neoplasias. The first group included 26 B-cell malignancies of various histologic subtypes containing a relatively high number of chromosomal changes and mostly mutated IgVH genes. This cluster displayed three cytogenetic branches, one with rearrangements in 7q, another with deletions in 17p and a third one with rearrangements in 1q and deletions in 6q and 13q. The second group included 19 cases, mostly diagnosed as B-cell chronic lymphocytic leukemia (B-CLL), and characterized by few additional chromosomal changes (e.g. trisomy 12) and unmutated IgVH genes. In conclusion, our study indicates that BCL3 translocations are not restricted to B-CLL but present in a heterogeneous group of B-cell malignancies.
Martín-Subero
J I
JI
Institute of Human Genetics, University Hospital Schleswig-Holstein Campus Kiel, Christian-Albrechts University, Kiel, Germany.
Ibbotson
R
R
Klapper
W
W
Michaux
L
L
Callet-Bauchu
E
E
Berger
F
F
Calasanz
M J
MJ
De Wolf-Peeters
C
C
Dyer
M J
MJ
Felman
P
P
Gardiner
A
A
Gascoyne
R D
RD
Gesk
S
S
Harder
L
L
Horsman
D E
DE
Kneba
M
M
Küppers
R
R
Majid
A
A
Parry-Jones
N
N
Ritgen
M
M
Salido
M
M
Solé
F
F
Thiel
G
G
Wacker
H-H
HH
Oscier
D
D
Wlodarska
I
I
Siebert
R
R
D000328:Adult; D000368:Aged; D000081242:B-Cell Lymphoma 3 Protein; D002883:Chromosomes, Human, Pair 14; D002888:Chromosomes, Human, Pair 19; D020732:Cytogenetic Analysis; D005260:Female; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin; D006651:Histocytochemistry; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015448:Leukemia, B-Cell / Q000145:classification / Q000235:genetics* / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000145:classification / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic
D000081242:B-Cell Lymphoma 3 Protein; C000631344:BCL3 protein, human; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors