Evolution and structure of clinically relevant gene fusions in multiple myeloma

Steven M. Foltz, Qingsong Gao, Christopher J. Yoon, Hua Sun, Lijun Yao, Yize Li, Reyka G. Jayasinghe, Song Cao, Justin King, Daniel R. Kohnen, Mark A. Fiala, Li Ding () and Ravi Vij ()
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Steven M. Foltz: Washington University in St. Louis
Qingsong Gao: Washington University in St. Louis
Christopher J. Yoon: Washington University in St. Louis
Hua Sun: Washington University in St. Louis
Lijun Yao: Washington University in St. Louis
Yize Li: Washington University in St. Louis
Reyka G. Jayasinghe: Washington University in St. Louis
Song Cao: Washington University in St. Louis
Justin King: Washington University in St. Louis
Daniel R. Kohnen: Washington University in St. Louis
Mark A. Fiala: Washington University in St. Louis
Li Ding: Washington University in St. Louis
Ravi Vij: Washington University in St. Louis

Nature Communications, 2020, vol. 11, issue 1, 1-12

Abstract: Abstract Multiple myeloma is a plasma cell blood cancer with frequent chromosomal translocations leading to gene fusions. To determine the clinical relevance of fusion events, we detect gene fusions from a cohort of 742 patients from the Multiple Myeloma Research Foundation CoMMpass Study. Patients with multiple clinic visits enable us to track tumor and fusion evolution, and cases with matching peripheral blood and bone marrow samples allow us to evaluate the concordance of fusion calls in patients with high tumor burden. We examine the joint upregulation of WHSC1 and FGFR3 in samples with t(4;14)-related fusions, and we illustrate a method for detecting fusions from single cell RNA-seq. We report fusions at MYC and a neighboring gene, PVT1, which are related to MYC translocations and associated with divergent progression-free survival patterns. Finally, we find that 4% of patients may be eligible for targeted fusion therapies, including three with an NTRK1 fusion.

Date: 2020
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DOI: 10.1038/s41467-020-16434-y

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