Weniger Marc A, Gesk Stefan, Ehrlich Steve, Martin-Subero José I, Dyer Martin J S, Siebert Reiner, Möller Peter, Barth Thomas F E
Department of Pathology, University of Ulm, Ulm, Germany.
Genes Chromosomes Cancer. 2007 Apr;46(4):406-15. doi: 10.1002/gcc.20420.
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.
REL基因座的扩增或增益在原发性纵隔B细胞淋巴瘤（PMBL）中很常见。在经典霍奇金淋巴瘤中，REL的基因组过度表达与核REL蛋白积累相关。为了研究PMBL中REL基因拷贝与其RNA和蛋白质表达之间的相关性，我们分析了20例PMBL以及PMBL衍生细胞系MedB-1和Karpas1106P的基因组、转录和蛋白质水平。通过荧光原位杂交（FISH），我们发现75%的PMBL存在增益/扩增，且PMBL细胞系中基因组REL过度表达。5例扩增的PMBL中有3例显示REL转录本升高，而通过实时PCR检测，10例增益的PMBL中只有3例显示REL转录本增加。1例无增益的PMBL显示REL转录增加。除1例尽管获得REL但免疫组化完全阴性的病例外，REL蛋白表达在PMBL中呈现出可变模式。尽管淋巴瘤细胞系中的转录水平普遍较低且核REL染色较弱，但这些细胞系仍表现出高NF-κB激活。通过荧光免疫表型分析和间期细胞遗传学作为肿瘤研究工具，REL的基因组增益/扩增与核REL表达显著相关（P < 0.05）。总之，PMBL中REL频繁的基因组过度表达不一定会引发REL转录/翻译增加。然而，基因组和蛋白质联合分析显示，在单细胞水平上，获得的REL与核REL积累存在显著关联。
