Mutational landscape in Waldenström macroglobulinemia evaluated using a next-generation sequencing lymphoma panel in routine clinical practice

Abstract

Next-generation sequencing (NGS) affords comprehensive insights into the genomic landscape of lymphomas. We examined the mutational pattern in patients with Waldenström macroglobulinemia (WM) or lymphoplasmacytic lymphoma (LPL) as well as the diagnostic and clinical utility of a tailored NGS lymphoma panel. A consecutive series of 45 patients was reviewed and NGS analysis was performed as part of a routine diagnostic setup. The custom designed NGS panel assayed all coding sequences of 59 genes of known clinical significance in lymphoid neoplasms. The most frequently mutated genes were MYD88, CXCR4, BIRC3, CD79B, and ARID1A. Additional somatic mutations were detected in 17 genes with four mutations categorized as pathogenic or likely pathogenic. BIRC3 and TP53 mutations were associated with adverse clinical phenotypes. NGS performance for the MYD88^L265P variant was 96% when compared to qPCR. In conclusion, targeted NGS provided important diagnostic and prognostic information in a routine clinical setting.

Keywords:

• Waldenström macroglobulinemia
• next-generation sequencing
• MYD88
• somatic mutation
• histological transformation

Acknowledgments

We would like to thank the molecular biology laboratory core facility at the Department of Pathology, Herlev University Hospital, Denmark for performing the NGS analyses.

Disclosure statement

The authors report there are no competing interests to declare.

Author contributions

SØ contributed to research design, the acquisition of data, analysis of data, and wrote the manuscript. LS, MFB, MØP, PN, EH, and LMRG contributed to research design, analysis of data, and provided NGS data or pathology review. THN contributed to research design, collection of data, and analysis of data. TH and LM contributed to research design and interpretation of data. All authors critically revised the article and approved the submitted version.

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request, and with the appropriate approvals of the Danish Research Ethics Committee.