B-cell lymphoma (BCL) is the most common hematologic malignancy. PiggyBac transposon tools to study clonal B-cell lymphomagenesis has been developed by researcher group including members of the University Institute of Translational Medicine. Cross-species analyses showed the efficiency of the screen to pinpoint human cancer drivers altered by non-genetic mechanisms, including clinically relevant genes dysregulated epigenetically, transcriptionally, or post-transcriptionally in human BCL. It has been also described a CRISPR/Cas9-based in vivo platform for BCL functional genomics, and validate discovered genes.