By exploring two independent clinical cohorts of DLBCL transcriptomic data, we reveal that low GNAS expression is associated with a high level of baseline TE expression and upregulated IFN signaling, and shares common disrupted biological activities in histone modification, mRNA processing, and transcriptional regulation with GNAS KO DLBCL cells. Here, IFNA1 is linked to diffuse large B-cell lymphoma.