Genetic interrogation of circulating multiple myeloma cells at single-cell resolution

Jens G. Lohr; Sora Kim; Joshua Gould; Birgit Knoechel; Yotam Drier; Matthew J. Cotton; Daniel Gray; Nicole Birrer; Bang Wong; Gavin Ha; Cheng Zhong Zhang; Guangwu Guo; Matthew Meyerson; Andrew J. Yee; Jesse S. Boehm; Noopur Raje; Todd R. Golub

doi:10.1126/scitranslmed.aac7037

Genetic interrogation of circulating multiple myeloma cells at single-cell resolution

Jens G. Lohr^*, Sora Kim, Joshua Gould, Birgit Knoechel, Yotam Drier, Matthew J. Cotton, Daniel Gray, Nicole Birrer, Bang Wong, Gavin Ha, Cheng Zhong Zhang, Guangwu Guo, Matthew Meyerson, Andrew J. Yee, Jesse S. Boehm, Noopur Raje, Todd R. Golub

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

120 Scopus citations

Abstract

Multiple myeloma (MM) remains an incurable disease, with a treatment-refractory state eventually developing in all patients. Constant clonal evolution and genetic heterogeneity of MM are a likely explanation for the emergence of drug-resistant disease. Monitoring ofMMgenomic evolution on therapy by serial bone marrowbiopsy is unfortunately impractical because it involves an invasive and painful procedure. We describe how noninvasive and highly sensitive isolation and characterization of circulating tumor cells (CTCs) from peripheral blood at single-cell resolution recapitulateMMin the bone marrow. We demonstrate that CTCs provide the same genetic information as bonemarrowMM cells and even reveal mutations with greater sensitivity than bone marrow biopsies in some cases. Single CTC RNA sequencing enables classification of MM and quantitative assessment of genes that are relevant for prognosis. We propose that the genomic characterization of CTCs should be included in clinical trials to follow the emergence of resistant subclones after MM therapy.2016

Original language	English
Article number	363ra147
Journal	Science Translational Medicine
Volume	8
Issue number	363
DOIs	https://doi.org/10.1126/scitranslmed.aac7037
State	Published - 2 Nov 2016
Externally published	Yes

Bibliographical note

Publisher Copyright:
© The Authors, some rights reserved;.

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Lohr, J. G., Kim, S., Gould, J., Knoechel, B., Drier, Y., Cotton, M. J., Gray, D., Birrer, N., Wong, B., Ha, G., Zhang, C. Z., Guo, G., Meyerson, M., Yee, A. J., Boehm, J. S., Raje, N., & Golub, T. R. (2016). Genetic interrogation of circulating multiple myeloma cells at single-cell resolution. Science Translational Medicine, 8(363), Article 363ra147. https://doi.org/10.1126/scitranslmed.aac7037

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abstract = "Multiple myeloma (MM) remains an incurable disease, with a treatment-refractory state eventually developing in all patients. Constant clonal evolution and genetic heterogeneity of MM are a likely explanation for the emergence of drug-resistant disease. Monitoring ofMMgenomic evolution on therapy by serial bone marrowbiopsy is unfortunately impractical because it involves an invasive and painful procedure. We describe how noninvasive and highly sensitive isolation and characterization of circulating tumor cells (CTCs) from peripheral blood at single-cell resolution recapitulateMMin the bone marrow. We demonstrate that CTCs provide the same genetic information as bonemarrowMM cells and even reveal mutations with greater sensitivity than bone marrow biopsies in some cases. Single CTC RNA sequencing enables classification of MM and quantitative assessment of genes that are relevant for prognosis. We propose that the genomic characterization of CTCs should be included in clinical trials to follow the emergence of resistant subclones after MM therapy.2016",

author = "Lohr, {Jens G.} and Sora Kim and Joshua Gould and Birgit Knoechel and Yotam Drier and Cotton, {Matthew J.} and Daniel Gray and Nicole Birrer and Bang Wong and Gavin Ha and Zhang, {Cheng Zhong} and Guangwu Guo and Matthew Meyerson and Yee, {Andrew J.} and Boehm, {Jesse S.} and Noopur Raje and Golub, {Todd R.}",

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doi = "10.1126/scitranslmed.aac7037",

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AU - Kim, Sora

AU - Gould, Joshua

AU - Knoechel, Birgit

AU - Drier, Yotam

AU - Cotton, Matthew J.

AU - Gray, Daniel

AU - Birrer, Nicole

AU - Wong, Bang

AU - Ha, Gavin

AU - Zhang, Cheng Zhong

AU - Guo, Guangwu

AU - Meyerson, Matthew

AU - Yee, Andrew J.

AU - Boehm, Jesse S.

AU - Raje, Noopur

AU - Golub, Todd R.

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AB - Multiple myeloma (MM) remains an incurable disease, with a treatment-refractory state eventually developing in all patients. Constant clonal evolution and genetic heterogeneity of MM are a likely explanation for the emergence of drug-resistant disease. Monitoring ofMMgenomic evolution on therapy by serial bone marrowbiopsy is unfortunately impractical because it involves an invasive and painful procedure. We describe how noninvasive and highly sensitive isolation and characterization of circulating tumor cells (CTCs) from peripheral blood at single-cell resolution recapitulateMMin the bone marrow. We demonstrate that CTCs provide the same genetic information as bonemarrowMM cells and even reveal mutations with greater sensitivity than bone marrow biopsies in some cases. Single CTC RNA sequencing enables classification of MM and quantitative assessment of genes that are relevant for prognosis. We propose that the genomic characterization of CTCs should be included in clinical trials to follow the emergence of resistant subclones after MM therapy.2016

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Genetic interrogation of circulating multiple myeloma cells at single-cell resolution

Abstract

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