Whole genome sequencing demonstrates substantial pathophysiological differences of MYC rearrangements in patients with plasma cell myeloma and B-cell lymphoma

Abstract

MYC rearrangements (MYCr) occur in several B-cell neoplasms and impact disease progression and overall survival. We used whole genome sequencing (WGS) and whole transcriptome sequencing (WTS) to analyze and compare MYCr in different B-cell neoplasms. The MYCr features of cases with plasma cell myeloma (PCM) (n = 88) showed distinct characteristics compared to cases with mature B-cell lymphomas (n = 62, including Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL) and high grade lymphoma with MYC and BCL2 and/or BCL6 rearrangements (HGBL)): they were more complex and showed a wider variety of translocation partners and breakpoints. Additionally, unlike B-cell lymphomas, they showed no evidence of activation-induced deaminase (AID) involvement in the formation of MYCr with immunoglobolin heavy chain (IGH), indicating a different mechanism of origin. The different MYCr characteristics resulted in poor MYCr detection rates by fluorescence in situ hybridization of only 50% in PCM, compared to 94% in lymphoma.

Keywords:

• MYC rearrangement
• plasma cell myeloma
• lymphoma
• whole genome sequencing

Acknowledgments

The authors would like to thank all co-workers at the MLL Munich Leukemia Laboratory for their dedicated work and all physicians for providing samples and caring for patients as well as collecting data. The authors would also like to thank Prof. Dr. Yasser El-Sherbiny from Nottingham Trent University for his support and his insights.

Author contributions

SB, AS and CH designed the study, SB and CH interpreted the data, SB and AS wrote the manuscript. SB, AS and CH were responsible for chromosome banding and FISH analyses, WW, CB and MM for molecular and bioinformatic analyses, IF for analysis of clinical data, WK for immunophenotyping and TH for cytomorphologic analyses. All authors read and contributed to the final version of the manuscript.

Disclosure statement

CH, WK, and TH declare part ownership of Munich Leukemia Laboratory (MLL). SB, AA, MM, CB, IF and AS are employed by the MLL.

Data availability statement

For original data, please contact [email protected].