Transcriptional profiling of the nuclear factor-kappaB pathway identifies a subgroup of primary lymphoma of the central nervous system with low BCL10 expression.
Recent studies point to a role of nuclear factor (NF)-kappaB signaling in a subset of diffuse large B cell lymphomas. We have analyzed the expression of 21 genes encoding NF-kappaB family members, upstream modulators, and targets in 32 primary central nervous system lymphomas (PCNSLs) by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Compared with nonmalignant germinal center centroblasts, expression of BCL10, REL, IAP1, and TRAF1 was significantly lower in PCNSLs, whereas that of BAX, BCLXL, BCL2, MALT1, CARD9, CARD10, CARD11, CARD14, CCND2, cFLIP, RELA, RELB, NFKB1, NFKB2, and IRF4 was higher. Hierarchical clustering of gene expression data revealed two distinct subgroups of PCNSLs, which were characterized by significantly different transcriptional levels, predominantly of BCL10, but also of REL and IAP1. Thus, these quantitative RT-PCR data with expression of genes of the NF-kappaB family as well as NF-kappaB-regulated genes together with immunohistochemical detection of nuclear RELA and REL indicate activation of the NF-kappaB pathway in PCNSLs, which may contribute to their high proliferative activity and the low level of apoptosis.
Courts
Cornelius
C
Department of Neuropathology, University Hospital of Cologne, Cologne, Germany.
Montesinos-Rongen
Manuel
M
Martin-Subero
Jose Ignacio
JI
Brunn
Anna
A
Siemer
Dörte
D
Zühlke-Jenisch
Reina
R
Pels
Hendrik
H
Jürgens
Annika
A
Schlegel
Uwe
U
Schmidt-Wolf
Ingo G H
IG
Schaller
Carlo
C
Reifenberger
Guido
G
Sabel
Michael
M
Warnecke-Eberz
Ute
U
Wiestler
Otmar D
OD
Küppers
Ralf
R
Siebert
Reiner
R
Deckert
Martina
M
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D000074018:B-Cell CLL-Lymphoma 10 Protein; D001402:B-Lymphocytes / Q000378:metabolism; D016543:Central Nervous System Neoplasms / Q000145:classification* / Q000378:metabolism; D016000:Cluster Analysis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D008223:Lymphoma / Q000145:classification* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015398:Signal Transduction / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; D000074018:B-Cell CLL-Lymphoma 10 Protein; C118591:BCL10 protein, human; D016328:NF-kappa B