Gain of chromosome region 18q21 including the MALT1 gene is associated with the activated B-cell-like gene expression subtype and increased BCL2 gene dosage and protein expression in diffuse large B-cell lymphoma.
BACKGROUND
The aim of this study was to determine the impact of a gain of the MALT1 gene on gene expression and clinical parameters in diffuse large B-cell lymphoma.


METHODS
We analyzed 116 cases of diffuse large B-cell lymphoma by fluorescence in situ hybridization, array-based comparative genomic hybridization, and transcriptional profiling.


RESULTS
A gain of 18q21 including MALT1 was detected in 44 cases (38%) and was accompanied by a gain of BCL2 in 43 cases. All cases with a 18q21/MALT1 gain showed BCL2 protein whereas 79% in the group without a 18q21/MALT1 gain did so (p<0.001). Cases with 18q21/MALT1 gain more frequently showed an activated B-cell-like (ABC) gene expression signature (65%) than a germinal center B-cell-like (GCB) one (23%) (p<0.001). Ninety-eight genes including MALT1, BCL2, and some selected nuclear factor-kappaB target genes were differentially expressed between the two genetic groups of diffuse large B-cell lymphoma. By global testing of each chromosome, we identified 33 genes, all located on chromosome 18q, which were differentially expressed between the two genetic groups independently of the ABC/GCB status. In multivariate analysis, the 18q21/MALT1 status represented an independent negative prognostic factor for overall survival (p=0.03).


CONCLUSIONS
In diffuse large B-cell lymphoma, gain of 18q21 including MALT1 is significantly associated with differential expression of genes located on 18q, the ABC gene expression subtype, increased BCL2 gene and protein expression and might indicate an unfavorable prognosis.
Dierlamm
Judith
J
Department of Oncology and Hematology with the sections of Bone Marrow Transplantation and Pneumology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany. judith_dierlamm@yahoo.de
Murga Penas
Eva M
EM
Bentink
Stefan
S
Wessendorf
Swen
S
Berger
Hilmar
H
Hummel
Michael
M
Klapper
Wolfram
W
Lenze
Dido
D
Rosenwald
Andreas
A
Haralambieva
Eugenia
E
Ott
German
G
Cogliatti
Sergio B
SB
Möller
Peter
P
Schwaenen
Carsten
C
Stein
Harald
H
Löffler
Markus
M
Spang
Rainer
R
Trümper
Lorenz
L
Siebert
Reiner
R
D000368:Aged; D001402:B-Lymphocytes / Q000166:cytology*; D020169:Caspases / Q000235:genetics*; D002887:Chromosomes, Human, Pair 18; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; D009363:Neoplasm Proteins / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D014158:Transcription, Genetic
D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D020169:Caspases; C400109:MALT1 protein, human; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein