Analysis of differential gene expression in NFKBIE-mutated and non-mutated primary mediastinal B-cell lymphoma (PMBL) via NanoString mRNA expression profiling.

We recently reported a truncating deletion in the NFKBIE gene, which encodes IκBε, a negative feedback regulator of NF-κB, in clinically aggressive chronic lymphocytic leukemia (CLL). Preliminary data indicate enrichment of NFKBIE aberrations in other lymphoid malignancies, hence we screened a large patient cohort (n=1460) diagnosed with different lymphoid neoplasms. We observed a a remarkably high frequency of NFKBIE aberrations (46/203 cases, 22,7%) in primary mediastinal B-cell lymphoma (PMBL). The deletion was associated with a particular aggressive clinical course and reduced survival in multivariate analysis. With gene expression profiling (GEP) via the NanoString nCounter hybridization system and the NanoString GX Human PanCancer Pathway Panel including 30 additional custom genes, the aim of this analysis was to study the differential activation of various oncogenic pathways including NFKB-signaling in NFKBIE mutated vs. non-mutated PMBL. For mRNA profiling and gene expression analysis, RNA from paraffin-embedded primary PMBL tissue was available for 36 patients (21 wildype and 15 NFKBIE mutated samples). 29 samples (8 NFKBIE-mutated and 21 wildtype PMBL) passed RNA and data quality controls and were used for gene expression analysis. RNA was profiled using the NanoString GX Human PanCancer Pathway Panel including 30 additional custom genes.