Validation of the double-hit gene expression signature (DLBCL90) in an independent cohort of patients with diffuse large B-cell lymphoma of germinal center origin.

Abstract The prognosis of diffuse large B-cell lymphoma (DLBCL) has been associated with clinical parameters, cell of origin (COO), and various genetic aberrations. Recently, a NanoString gene expression assay (DLBCL90) was developed which identifies DLBCL cases with an outcome similar to those with double- or triple-hit DLBCL with both MYC and BCL2 rearrangements. We carried out this study to validate the predictive ability of the DLBCL90 assay in an independent cohort of patients with the germinal center B-cell (GCB) subtype DLBCL. We also used a customized targeted sequencing panel to analyze the mutational profile in these patients. Cases with a double- or triple-hit by conventional fluorescence in situ hybridization (FISH) cytogenetic analysis are known to have a poor prognosis and the DLBCL90 gene expression signature identified these cases, as well as additional cases that would have otherwise been missed by FISH analysis. Our findings validate use of the DLBCL90 assay for identifying high risk patients for new and innovative therapies.