Clinical impact of 5^ʹMYC or 3^ʹMYC 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^ʹMYC or 3^ʹMYC. 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^ʹMYC deletion (n = 16) or 3^ʹMYC deletion plus 5^ʹMYC amplification (n = 5), 5^ʹMYC gain (n = 10), 5^ʹMYC deletion (n = 3), and 3^ʹMYC gain (n = 1). For comparison, we also included 9 patients who showed an unbalanced MYC-R. Patients with 5^ʹMYC gain showed MYC expression and were often refractory to chemotherapy (n = 7) or had early relapse (n = 2). By contrast, lymphomas with 3^ʹMYC 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^ʹMYC deletion, 5^ʹMYC gain and unbalanced MYC-R, respectively (p = 0.0048). We conclude that 5^ʹMYC gain is associated with MYC expression and a poorer prognosis and likely represents an unbalanced MYC-R. By contrast, 3^ʹMYC deletions are not associated with MYC expression or a poorer prognosis and this finding may be unrelated to MYC-R.