Research Article| Volume 272, P1-8, April 2023

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


      • Atypical MYC FISH signal patterns (5’MYC or 3’MYC gain/loss) are not equivalent to unbalanced MYC-R.
      • 5’MYC gain often associates with refractory to chemotherapy and short event-free survival and likely represents an unbalanced MYC-R.
      • 3’MYC loss is not associated with poor prognosis and may not represent MYC-R.


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


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