Through RNA-seq and targeted exon sequencing analysis, investigators working in the CGCI program discovered FOXO1 frequently mutated in diffuse large B-cell lymphoma (DLBCL) cases. FOXO1 is a nuclear transcription factor that regulates genes involved in B-cell differentiation and other important cellular processes. Most of the recurrent FOXO1 mutations clustered within two N-terminal regions, and are predicted to disrupt interaction with negative regulator, 14-3-3. The investigators demonstrated an absence of 14-3-3 binding and other related phenotypes when they tested a few of the mutations. The FOXO1 mutations are associated with lower overall survival rates, especially among DLBCL patients identified as low-risk by the revised International Prognostic Index (R-IPI). Together, these results suggest the importance of FOXO1 in DLBCL pathogenesis and the possibility of using FOXO1 mutations as a prognostic indicator in DLBCL patients.