title: 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.
abstract: 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.
authors: 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
authors: Judith
authors: J
authors: Dierlamm
authors: Eva M
authors: EM
authors: Murga Penas
authors: Stefan
authors: S
authors: Bentink
authors: Swen
authors: S
authors: Wessendorf
authors: Hilmar
authors: H
authors: Berger
authors: Michael
authors: M
authors: Hummel
authors: Wolfram
authors: W
authors: Klapper
authors: Dido
authors: D
authors: Lenze
authors: Andreas
authors: A
authors: Rosenwald
authors: Eugenia
authors: E
authors: Haralambieva
authors: German
authors: G
authors: Ott
authors: Sergio B
authors: SB
authors: Cogliatti
authors: Peter
authors: P
authors: Möller
authors: Carsten
authors: C
authors: Schwaenen
authors: Harald
authors: H
authors: Stein
authors: Markus
authors: M
authors: Löffler
authors: Rainer
authors: R
authors: Spang
authors: Lorenz
authors: L
authors: Trümper
authors: Reiner
authors: R
authors: Siebert
mesh_terms: 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
chemical_list: 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