Transcriptional profiling of the nuclear factor-κB 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)-κB signaling in a subset of diffuse large B cell lymphomas. We have analyzed the expression of 21 genes encoding NF-κB 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-κB family as well as NF-κB-regulated genes together with immunohistochemical detection of nuclear RELA and REL indicate activation of the NF-κB pathway in PCNSLs, which may contribute to their high proliferative activity and the low level of apoptosis. © 2007 American Association of Neuropathologists, Inc.