Our current study revealed that HGBCL, NOS expressing DLBCL‐like signatures have higher genomic aberrations and are characterized by deletion of well‐characterized TSGs (e.g., PRDM1, CDKN2A, TP53, RB1), and recurrent mutations in MYD88 and PIM1 and may be therapeutically vulnerable to BCR and/or PIM1 inhibition as rational therapeutic approach. Here, PRDM1 is linked to diffuse large B-cell lymphoma.