Analyse des genomischen Status der Proto-Onkogene c-rel und bcl11a und deren RNA und Proteinexpression im mediastinalen (thymischen) B-Zell-Lymphom
Weniger, Marc Andrée
LicenseStandard (Fassung vom 03.05.2003)
Mediastinal (thymic) large B-cell lymphoma (MBL) is characterized by overrepresentations of chromosome 2p16 haboring the c-rel and bcl11a proto-oncogenes. Increased c-rel copies as well as co-amplifications of c-rel and bcl11a have been identified in several lymphomas. The increased expression of a product due to increased copies of the corresponding gene is referred to as gene dosage mechanism. Whether increased c-rel and/or bcl11a gene copies provoke increased RNA and protein expression is unclear. To assess a gene dosage mechanism for these genes 20 MBLs have been analysed for their gene, transcript, and protein levels using fluorescence in situ hybridization (FISH), quantitative real-time PCR (qRT-PCR), immunochemistry, and fluorescence immunophenotyping and interphase cytogenetics as tool for the investigation of neoplasms (FICTION). By FISH five and 10 MBLs showed amplifications and gains of c-rel and bcl11a, respectively. The highest c-rel and bcl11a transcript levels have been found in MBLs with amplifications by qRT-PCT. Genomic gains correlated with increased c-rel transcript levels in three and with increased bcl11a transcript levels in four MBLs, respectively. In one MBL with normal gene copies the c-rel transcript levels were increased. The c-Rel as well as Bcl11A-XL protein expressions were heterogeneous but largely positive irrespective of the genomic status and/or transcript levels. A strict gene dosage mechanism has been observed in one MBL for c-rel/c-Rel and three MBLs for bcl11a/Bcl11A-XL, respectively. By FICTION however increased c-rel copies correlated with nuclearly accumulated c-Rel. In conclusion 75% of MBLs showed simultaneously increased c-rel/bcl11a copies. The expression of c-Rel and Bcl11A-XL proteins irrespective of the gene dosage and/or transcript levels argues against a strict gene dosage mechanism in the majority of MBLs whereas FICTION demonstrated a clear correlation between c-rel copies and nuclear c-Rel protein.
Subject HeadingsLymphom [GND]
Nuklearfaktor Kappa B [GND]
Lymphoma, B-cell [MeSH]
Proto-oncogene proteins c-rel [MeSH]