PMID- 17243160 OWN - NLM STAT- MEDLINE DCOM- 20070418 LR - 20240109 IS - 1045-2257 (Print) IS - 1045-2257 (Linking) VI - 46 IP - 4 DP - 2007 Apr TI - Gains of REL in primary mediastinal B-cell lymphoma coincide with nuclear accumulation of REL protein. PG - 406-15 AB - Gains or amplifications of the REL locus are frequently seen in primary mediastinal B-cell lymphoma (PMBL). In classical Hodgkin's lymphoma, genomic overrepresentation of REL correlated with nuclear REL protein accumulation. To investigate the correlation between REL gene copies and its RNA and protein expression in PMBL, we analyzed genomic, transcriptional, and protein levels in 20 PMBLs and the PMBL derived cell lines MedB-1 and Karpas1106P. We found gains/amplifications in 75% of the PMBLs by fluorescence in situ hybridization (FISH) and genomic REL overrepresentation in the PMBL lines. Three of the five PMBLs with amplifications displayed elevated REL transcripts, while only 3/10 PMBLs with gains showed increased REL transcripts by real-time PCR. One PMBL without gains displayed increased REL transcription. REL protein expression exhibited a variable pattern across the PMBLs except for a single case that was completely negative by immunohistochemistry despite having gained REL. Although transcript levels were generally low and nuclear REL staining was weak in the lymphoma cell lines, these nevertheless exhibited high NF-kappaB activation. By fluorescence immunophenotyping and interphase cytogenetics as a tool for investigation of neoplasms, genomic gains/amplifications of REL significantly correlated with nuclear REL expression (P < 0.05). In conclusion, the frequent genomic overrepresentation of REL in PMBL does not necessarily trigger an increased transcription/translation of REL. However, combined genomic and protein analysis revealed a significant association of gained REL and nuclear REL accumulation at the single cell level. CI - (c) 2007 Wiley-Liss, Inc. FAU - Weniger, Marc A AU - Weniger MA AD - Department of Pathology, University of Ulm, Ulm, Germany. FAU - Gesk, Stefan AU - Gesk S FAU - Ehrlich, Steve AU - Ehrlich S FAU - Martin-Subero, Jose I AU - Martin-Subero JI FAU - Dyer, Martin J S AU - Dyer MJ FAU - Siebert, Reiner AU - Siebert R FAU - Moller, Peter AU - Moller P FAU - Barth, Thomas F E AU - Barth TF LA - eng GR - MC_U132670597/MRC_/Medical Research Council/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Genes Chromosomes Cancer JT - Genes, chromosomes & cancer JID - 9007329 RN - 0 (Proto-Oncogene Proteins c-rel) SB - IM MH - Cell Nucleus/*metabolism MH - Gene Expression Regulation, Neoplastic/physiology MH - Humans MH - Lymphoma, B-Cell/genetics/*metabolism MH - Mediastinal Neoplasms/genetics/*metabolism MH - Proto-Oncogene Proteins c-rel/genetics/*metabolism EDAT- 2007/01/24 09:00 MHDA- 2007/04/19 09:00 CRDT- 2007/01/24 09:00 PHST- 2007/01/24 09:00 [pubmed] PHST- 2007/04/19 09:00 [medline] PHST- 2007/01/24 09:00 [entrez] AID - 10.1002/gcc.20420 [doi] PST - ppublish SO - Genes Chromosomes Cancer. 2007 Apr;46(4):406-15. doi: 10.1002/gcc.20420.