The prognosis of translocation positive diffuse large B-cell lymphoma depends on the second hit.

A proportion of translocation positive diffuse large B-cell lymphomas (DLBCL) harbour a and/or translocation, known as double-hit DLBCL, and are clinically aggressive. It is unknown whether there are other genetic abnormalities that cooperate with translocation and form double-hit DLBCL, and whether there is a difference in clinical outcome between the double-hit DLBCL and those with an isolated translocation. We investigated gene mutations along with and translocations in a total of 234 cases of DLBCL, including 81 with translocation. mutations were investigated by PCR and sequencing, while and translocation was studied by interphase fluorescence in situ hybridization. The majority of translocation positive DLBCLs (60/81 = 74%) had at least one additional genetic hit. In translocation positive DLBCL treated by R-CHOP ( = 67), mutation and but not translocation had an adverse effect on patient overall survival. In comparison with DLBCL with an isolated translocation, cases with double-hits had the worst overall survival, followed by those with double-hits. In translocation negative DLBCL treated by R-CHOP ( = 101), mutation, and translocation had no impact on patient survival. The prognosis of translocation positive DLBCL critically depends on the second hit, with mutations and translocation contributing to an adverse prognosis. It is pivotal to investigate both mutations and translocations in translocation positive DLBCL, and to distinguish double-hit DLBCLs from those with an isolated translocation.