title: Gains of REL in primary mediastinal B-cell lymphoma coincide with nuclear accumulation of REL protein.
abstract: 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.
authors.affiliation: Department of Pathology, University of Ulm, Ulm, Germany.
authors.forename: Marc A
authors.initials: MA
authors.lastname: Weniger
authors.forename: Stefan
authors.initials: S
authors.lastname: Gesk
authors.forename: Steve
authors.initials: S
authors.lastname: Ehrlich
authors.forename: José I
authors.initials: JI
authors.lastname: Martin-Subero
authors.forename: Martin J S
authors.initials: MJ
authors.lastname: Dyer
authors.forename: Reiner
authors.initials: R
authors.lastname: Siebert
authors.forename: Peter
authors.initials: P
authors.lastname: Möller
authors.forename: Thomas F E
authors.initials: TF
authors.lastname: Barth
mesh_terms: D002467:Cell Nucleus / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000378:metabolism*; D008479:Mediastinal Neoplasms / Q000235:genetics / Q000378:metabolism*; D020569:Proto-Oncogene Proteins c-rel / Q000235:genetics / Q000378:metabolism*
chemical_list: D020569:Proto-Oncogene Proteins c-rel