An increase in <i>MYC</i> 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

Abstract

<i>MYC</i> 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 <i>MYC</i> have also been detected in these patients, but their incidence and prognostic role are still controversial. We analyzed the clinical impact of <i>MYC</i> increased copy number on 385 patients with diffuse large B-cell lymphoma screened at diagnosis for <i>MYC</i>, <i>BCL2</i>, and <i>BCL6</i> rearrangements. We enumerated the number of <i>MYC</i> copies, defining as amplified those cases with an uncountable number of extra-copies. The prevalence of <i>MYC</i> 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 <i>MYC</i> 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 <i>MYC</i> extra-copies showed a negative correlation between an increasing number of copies and survival. Patients with >7 copies or the amplification of <i>MYC</i> had the poorest prognosis. Patients with >4 copies of MYC showed a similar, trending towards worse prognosis compared to patients with <i>MYC</i> translocation. The survival of patients with >4 copies, translocation or amplification of <i>MYC</i> seemed to be superior if intensive treatments were used. Our study underlines the importance of fluorescence <i>in situ</i> hybridization testing at diagnosis of diffuse large B-cell lymphoma to detect the rather frequent and clinically significant numerical aberrations of <i>MYC</i>.