title: Transcriptional profiling of the nuclear factor-kappaB pathway identifies a subgroup of primary lymphoma of the central nervous system with low BCL10 expression.
abstract: 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.
authors.affiliation: Department of Neuropathology, University Hospital of Cologne, Cologne, Germany.
authors.forename: Cornelius
authors.initials: C
authors.lastname: Courts
authors.forename: Manuel
authors.initials: M
authors.lastname: Montesinos-Rongen
authors.forename: Jose Ignacio
authors.initials: JI
authors.lastname: Martin-Subero
authors.forename: Anna
authors.initials: A
authors.lastname: Brunn
authors.forename: Dörte
authors.initials: D
authors.lastname: Siemer
authors.forename: Reina
authors.initials: R
authors.lastname: Zühlke-Jenisch
authors.forename: Hendrik
authors.initials: H
authors.lastname: Pels
authors.forename: Annika
authors.initials: A
authors.lastname: Jürgens
authors.forename: Uwe
authors.initials: U
authors.lastname: Schlegel
authors.forename: Ingo G H
authors.initials: IG
authors.lastname: Schmidt-Wolf
authors.forename: Carlo
authors.initials: C
authors.lastname: Schaller
authors.forename: Guido
authors.initials: G
authors.lastname: Reifenberger
authors.forename: Michael
authors.initials: M
authors.lastname: Sabel
authors.forename: Ute
authors.initials: U
authors.lastname: Warnecke-Eberz
authors.forename: Otmar D
authors.initials: OD
authors.lastname: Wiestler
authors.forename: Ralf
authors.initials: R
authors.lastname: Küppers
authors.forename: Reiner
authors.initials: R
authors.lastname: Siebert
authors.forename: Martina
authors.initials: M
authors.lastname: Deckert
mesh_terms: 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*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000074018:B-Cell CLL-Lymphoma 10 Protein; C118591:BCL10 protein, human; D016328:NF-kappa B