Clinical impact of 5^'MYC or 3^'MYC gain/loss detected by FISH in patients with aggressive B-cell lymphomas

FISH analysis using MYC break-apart probes is a widely used technique to assess for MYC rearrangement (MYC-R). Occasionally, FISH results in atypical signal patterns, such as gain or loss of 5^'MYC or 3^'MYC. The clinical impact and/or relationship of these atypical signal patterns to MYC-R are unknown. In this study, we assessed 35 patients who had aggressive B-cell lymphomas and exhibited atypical FISH signal patterns: 3^'MYC deletion (n = 16) or 3^'MYC deletion plus 5^'MYC amplification (n = 5), 5^'MYC gain (n = 10), 5^'MYC deletion (n = 3), and 3^'MYC gain (n = 1). For comparison, we also included 9 patients who showed an unbalanced MYC-R. Patients with 5^'MYC gain showed MYC expression and were often refractory to chemotherapy (n = 7) or had early relapse (n = 2). By contrast, lymphomas with 3^'MYC deletion were negative or had low expression of MYC (16 of 18), and patients often responded to chemotherapy (16 of 19). The median event-free survival was 24, 6, and 4 months for patients with 3^'MYC deletion, 5^'MYC gain and unbalanced MYC-R, respectively (p = 0.0048). We conclude that 5^'MYC gain is associated with MYC expression and a poorer prognosis and likely represents an unbalanced MYC-R. By contrast, 3^'MYC deletions are not associated with MYC expression or a poorer prognosis and this finding may be unrelated to MYC-R.