An increase in copy number has a progressive negative prognostic impact in patients with diffuse large B-cell and high-grade lymphoma, who may benefit from intensified treatment regimens.

translocations, a hallmark of Burkitt lymphoma, occur in 5-15% of diffuse large B-cell lymphoma, and have a negative prognostic impact. Numerical aberrations of have also been detected in these patients, but their incidence and prognostic role are still controversial. We analyzed the clinical impact of increased copy number on 385 patients with diffuse large B-cell lymphoma screened at diagnosis for , , and rearrangements. We enumerated the number of copies, defining as amplified those cases with an uncountable number of extra-copies. The prevalence of translocation, increased copy number and amplification was 8.8%, 15%, and 1%, respectively. Patients with 3 or 4 gene copies, accounting for more than 60% of patients with copy number changes, had a more favorable outcome compared to patients with >4 copies or translocation of MYC, and were not influenced by the type of treatment received as first-line. Stratification according to the number of extra-copies showed a negative correlation between an increasing number of copies and survival. Patients with >7 copies or the amplification of had the poorest prognosis. Patients with >4 copies of MYC showed a similar, trending towards worse prognosis compared to patients with translocation. The survival of patients with >4 copies, translocation or amplification of seemed to be superior if intensive treatments were used. Our study underlines the importance of fluorescence hybridization testing at diagnosis of diffuse large B-cell lymphoma to detect the rather frequent and clinically significant numerical aberrations of .