Synapse - Accelerated single cell seeding in relapsed multiple myeloma

Accelerated single cell seeding in relapsed multiple myeloma Journal Article

Authors:	Landau, H. J.; Yellapantula, V.; Diamond, B. T.; Rustad, E. H.; Maclachlan, K. H.; Gundem, G.; Medina-Martinez, J.; Arango Ossa, J.; Levine, M. F.; Zhou, Y.; Kappagantula, R.; Baez, P.; Attiye, M.; Makohon-Moore, A.; Zhang, L.; Boyle, E. M.; Ashby, C.; Blaney, P.; Patel, M.; Zhang, Y.; Dogan, A.; Chung, D. J.; Giralt, S.; Lahoud, O. B.; Peled, J. U.; Scordo, M.; Shah, G.; Hassoun, H.; Korde, N. S.; Lesokhin, A. M.; Lu, S.; Mailankody, S.; Shah, U.; Smith, E.; Hultcrantz, M. L.; Ulaner, G. A.; van Rhee, F.; Morgan, G. J.; Landgren, O.; Papaemmanuil, E.; Iacobuzio-Donahue, C.; Maura, F.
Article Title:	Accelerated single cell seeding in relapsed multiple myeloma
Abstract:	Multiple myeloma (MM) progression is characterized by the seeding of cancer cells in different anatomic sites. To characterize this evolutionary process, we interrogated, by whole genome sequencing, 25 samples collected at autopsy from 4 patients with relapsed MM and an additional set of 125 whole exomes collected from 51 patients. Mutational signatures analysis showed how cytotoxic agents introduce hundreds of unique mutations in each surviving cancer cell, detectable by bulk sequencing only in cases of clonal expansion of a single cancer cell bearing the mutational signature. Thus, a unique, single-cell genomic barcode can link chemotherapy exposure to a discrete time window in a patient′s life. We leveraged this concept to show that MM systemic seeding is accelerated at relapse and appears to be driven by the survival and subsequent expansion of a single myeloma cell following treatment with high-dose melphalan therapy and autologous stem cell transplant. © 2020, The Author(s).
Keywords:	survival; cancer chemotherapy; clinical article; survival analysis; gene sequence; overall survival; sequence analysis; single nucleotide polymorphism; lenalidomide; cancer recurrence; cisplatin; doxorubicin; chemotherapy; bortezomib; multiple myeloma; etoposide; cohort analysis; genetic variability; cyclophosphamide; dexamethasone; melphalan; autologous stem cell transplantation; tumor biopsy; validation study; mutational analysis; cancer research; risk factor; fluorodeoxyglucose f 18; platinum; genome; tumor; autopsy; bioinformatics; disease exacerbation; carfilzomib; programmed death 1 ligand 1; cell; copy number variation; single cell analysis; nucleic acid base substitution; phylogenetic tree; maximum standardized uptake value; pomalidomide; cancer; human; article; whole genome sequencing; copy number aberration; daratumumab; mutational load; positron emission tomography-computed tomography; disease seeding; stem cell transplantion
Journal Title:	Nature Communications
Volume:	11
ISSN:	2041-1723
Publisher:	Nature Publishing Group
Date Published:	2020-07-17
Start Page:	3617
Language:	English
DOI:	10.1038/s41467-020-17459-z
PUBMED:	32680998
PROVIDER:	scopus
PMCID:	PMC7368016
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85088126947&doi=10.1038%2fs41467-020-17459-z&partnerID=40&md5=f9d58d742826ce2bf33acd79f8b90ed8
Notes:	Article -- Correction issued, see DOI: 10.1038/s41467-021-20978-y -- Export Date: 3 August 2020 -- Source: Scopus