Characterization of Richter-transformed lymphoma and genomic instability as a potential vulnerability in 17p-deleted lymphomas

Here, we focus on two distinct diffuse large B-cell lymphoma (DLBCL) subtypes with poor prognosis, DLBCLs with biallelic TP53 inactivation and DLBCLs that arise through Richter transformation (RT) from chronic lymphocytic leukemia (CLL). By applying an integrative multi-omics and multi-platform approach we will characterize the molecular landscape of RT DLBCLs and define cell-autonomous and non-cell-autonomous oncogenic determinants and associated survival pathways of both lymphomas. Longitudinal assessment of alterations in CLL and paired RT-DLBCLs and an in vivo insertional mutagenesis screen will provide mechanistic insights into the molecular basis of RT that will guide our modelling and future targeting strategies.