Prognostic significance of copy number gains of MYC detected by fluorescence in situ hybridization in large B-cell lymphoma

Abstract

The MYC protooncogene plays a critical role in many cellular processes. MYC translocations are recurrent in large B-cell lymphomas (LBCLs) where they exhibit a negative effect on survival. Gain of MYC copies is also frequently identified; however, there is no consensus on the frequency and prognostic significance of MYC copy gains. We collected FISH data for MYC with reflex testing for BCL2 and BCL6 and IHC results at diagnosis for a cohort of 396 de novo and transformed LBCL cases and compared progression-free (PFS) and overall survival (OS) to determine the prognostic impact of extra MYC copies. The prevalence of cases with MYC copy number gain was 20.9%. PFS was shorter for patients with ≥5 MYC copies compared to controls (p = 0.0005, HR = 2.25). .MYC gain trended towards worse OS; patients with ≥7MYC copies had worse OS (p = 0.013), similar to patients with MYC translocations. We propose that MYC gain represents a dose-dependent prognostic factor for LBCLs.

Keywords:

• Large B-cell lymphoma
• mYC
• copy number

Acknowledgments

The authors would like to thank the staff of the cytogenetics laboratory for their technical expertise.

Author’s contribution

Contribution: M.S. undertook concept and design; T.Z., L.S.S and M.S. collected data; T.Z., L.S.S., R.K. and M.S. undertook data analysis and interpretation; T.Z., L.S.S. and M.S. wrote the manuscript; J.G., A.B., X.L reviewed the manuscript and provided critics, and all authors edited the article and provided final approval.

Disclosure statement

The authors declare no competing financial interests in relation to the work described.ORCID profile: M.S. 0000-0002-1843-7038.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.