MinimuMM-seq: Genome Sequencing of Circulating Tumor Cells for Minimally Invasive Molecular Characterization of Multiple Myeloma Pathology.

Autor:	Dutta AK; Center for Prevention of Progression of Blood Cancers, Dana-Farber Cancer Institute, Boston, Massachusetts.; Department of Medical Oncology, Harvard Medical School, Boston, Massachusetts.; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts., Alberge JB; Center for Prevention of Progression of Blood Cancers, Dana-Farber Cancer Institute, Boston, Massachusetts.; Department of Medical Oncology, Harvard Medical School, Boston, Massachusetts.; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts., Lightbody ED; Center for Prevention of Progression of Blood Cancers, Dana-Farber Cancer Institute, Boston, Massachusetts.; Department of Medical Oncology, Harvard Medical School, Boston, Massachusetts.; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts., Boehner CJ; Center for Prevention of Progression of Blood Cancers, Dana-Farber Cancer Institute, Boston, Massachusetts.; Department of Medical Oncology, Harvard Medical School, Boston, Massachusetts.; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts., Dunford A; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts., Sklavenitis-Pistofidis R; Center for Prevention of Progression of Blood Cancers, Dana-Farber Cancer Institute, Boston, Massachusetts.; Department of Medical Oncology, Harvard Medical School, Boston, Massachusetts.; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts., Mouhieddine TH; Center for Prevention of Progression of Blood Cancers, Dana-Farber Cancer Institute, Boston, Massachusetts.; Department of Medical Oncology, Harvard Medical School, Boston, Massachusetts.; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts., Cowan AN; Center for Prevention of Progression of Blood Cancers, Dana-Farber Cancer Institute, Boston, Massachusetts.; Department of Medical Oncology, Harvard Medical School, Boston, Massachusetts., Su NK; Center for Prevention of Progression of Blood Cancers, Dana-Farber Cancer Institute, Boston, Massachusetts.; Department of Medical Oncology, Harvard Medical School, Boston, Massachusetts.; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts., Horowitz EM; Center for Prevention of Progression of Blood Cancers, Dana-Farber Cancer Institute, Boston, Massachusetts.; Department of Medical Oncology, Harvard Medical School, Boston, Massachusetts., Barr H; Center for Prevention of Progression of Blood Cancers, Dana-Farber Cancer Institute, Boston, Massachusetts.; Department of Medical Oncology, Harvard Medical School, Boston, Massachusetts., Hevenor L; Center for Prevention of Progression of Blood Cancers, Dana-Farber Cancer Institute, Boston, Massachusetts.; Department of Medical Oncology, Harvard Medical School, Boston, Massachusetts., Beckwith JB; Center for Prevention of Progression of Blood Cancers, Dana-Farber Cancer Institute, Boston, Massachusetts.; Department of Medical Oncology, Harvard Medical School, Boston, Massachusetts., Perry J; Center for Prevention of Progression of Blood Cancers, Dana-Farber Cancer Institute, Boston, Massachusetts.; Department of Medical Oncology, Harvard Medical School, Boston, Massachusetts., Cao A; Center for Prevention of Progression of Blood Cancers, Dana-Farber Cancer Institute, Boston, Massachusetts.; Department of Medical Oncology, Harvard Medical School, Boston, Massachusetts., Lin Z; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts., Kuhr FK; Menarini Silicon Biosystems, Huntingdon Valley, Pennsylvania., Mastro RGD; Menarini Silicon Biosystems, Huntingdon Valley, Pennsylvania., Nadeem O; Center for Prevention of Progression of Blood Cancers, Dana-Farber Cancer Institute, Boston, Massachusetts.; Department of Medical Oncology, Harvard Medical School, Boston, Massachusetts., Greipp PT; Department of Laboratory Medicine and Pathology, Mayo Clinic Comprehensive Cancer Center, Rochester, Minnesota., Stewart C; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts., Auclair D; Multiple Myeloma Research Foundation, Norwalk, Connecticut., Getz G; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts.; Cancer Center and Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts., Ghobrial IM; Center for Prevention of Progression of Blood Cancers, Dana-Farber Cancer Institute, Boston, Massachusetts.; Department of Medical Oncology, Harvard Medical School, Boston, Massachusetts.; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts.
Jazyk:	angličtina
Zdroj:	Cancer discovery [Cancer Discov] 2023 Feb 06; Vol. 13 (2), pp. 348-363.
DOI:	10.1158/2159-8290.CD-22-0482
Abstrakt:	Multiple myeloma (MM) develops from well-defined precursor stages; however, invasive bone marrow (BM) biopsy limits screening and monitoring strategies for patients. We enumerated circulating tumor cells (CTC) from 261 patients (84 monoclonal gammopathy of undetermined significance, 155 smoldering multiple myeloma, and 22 MM), with neoplastic cells detected in 84%. We developed a novel approach, MinimuMM-seq, which enables the detection of translocations and copy-number abnormalities through whole-genome sequencing of highly pure CTCs. Application to CTCs in a cohort of 51 patients, 24 with paired BM, was able to detect 100% of clinically reported BM biopsy events and could replace molecular cytogenetics for diagnostic yield and risk classification. Longitudinal sampling of CTCs in 8 patients revealed major clones could be tracked in the blood, with clonal evolution and shifting dynamics of subclones over time. Our findings provide proof of concept that CTC detection and genomic profiling could be used clinically for monitoring and managing disease in MM. Significance: In this study, we established an approach enabling the enumeration and sequencing of CTCs to replace standard molecular cytogenetics. CTCs harbored the same pathognomonic MM abnormalities as BM plasma cells. Longitudinal sampling of serial CTCs was able to track clonal dynamics over time and detect the emergence of high-risk genetic subclones. This article is highlighted in the In This Issue feature, p. 247. (©2022 American Association for Cancer Research.)
Databáze:	MEDLINE
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