TY - JOUR
T1 - Evolution and structure of clinically relevant gene fusions in multiple myeloma
AU - Foltz, Steven M.
AU - Gao, Qingsong
AU - Yoon, Christopher J.
AU - Sun, Hua
AU - Yao, Lijun
AU - Li, Yize
AU - Jayasinghe, Reyka G.
AU - Cao, Song
AU - King, Justin
AU - Kohnen, Daniel R.
AU - Fiala, Mark A.
AU - Ding, Li
AU - Vij, Ravi
N1 - Funding Information:
This work has been supported by the Paula C. and Rodger O. Riney Blood Cancer Research Initiative Fund to L.D. and R.V. and NCI U24CA211006 and U2CCA233303 funds to L.D. We also thank the patients, families, and professionals who have contributed to the Multiple Myeloma Research Foundation CoMMpass Study.
Funding Information:
Top recurrent fusions supported by WGS (Number of samples)
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85085701765&partnerID=8YFLogxK
U2 - 10.1038/s41467-020-16434-y
DO - 10.1038/s41467-020-16434-y
M3 - Article
C2 - 32471990
AN - SCOPUS:85085701765
SN - 2041-1723
VL - 11
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 2666
ER -