Baseline identification of clonal V(D)J sequences for DNA-based minimal residual disease detection in multiple myeloma Journal Article


Authors: Rustad, E. H.; Hultcrantz, M.; Yellapantula, V. D.; Akhlaghi, T.; Ho, C.; Arcila, M. E.; Roshal, M.; Patel, A.; Chen, D.; Devlin, S. M.; Jacobsen, A.; Huang, Y.; Miller, J. E.; Papaemmanuil, E.; Landgren, O.
Article Title: Baseline identification of clonal V(D)J sequences for DNA-based minimal residual disease detection in multiple myeloma
Abstract: Tracking of clonal immunoglobulin V(D)J rearrangement sequences by next generation sequencing is highly sensitive for minimal residual disease in multiple myeloma. However, previous studies have found variable rates of V(D)J sequence identification at baseline, which could limit tracking. Here, we aimed to define the factors influencing the identification of clonal V(D)J sequences. Bone marrow mononuclear cells from 177 myeloma patients underwent V(D)J sequencing by the LymphoTrack assays (Invivoscribe). As a molecular control for tumor cell content, we sequenced the samples using our in-house myeloma panel myTYPE. V(D)J sequence clonality was identified in 81% of samples overall, as compared with 95% in samples where tumor-derived DNA was detectable by myTYPE. Clonality was detected more frequently in patients with lambda-restricted disease, mainly because of increased detection of kappa gene rearrangements. Finally, we describe how the tumor cell content of bone marrow aspirates decrease gradually in sequential pulls because of hemodilution: From the initial pull used for aspirate smear, to the final pull that is commonly used for research. In conclusion, baseline clonality detection rates of 95% or higher are feasible in multiple myeloma. Optimal performance depends on the use of good quality aspirates and/or subsequent tumor cell enrichment. © 2019 Rustad et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: adult; controlled study; human tissue; aged; human cell; major clinical study; sequence analysis; polymerase chain reaction; multiple myeloma; retrospective study; hemodilution; feasibility study; dna; gene rearrangement; clonal variation; bone marrow biopsy; minimal residual disease; dna determination; vdj recombination; human; male; female; article; bone marrow derived mononuclear cell
Journal Title: PLoS ONE
Volume: 14
Issue: 3
ISSN: 1932-6203
Publisher: Public Library of Science  
Date Published: 2019-03-22
Start Page: e0211600
Language: English
DOI: 10.1371/journal.pone.0211600
PUBMED: 30901326
PROVIDER: scopus
PMCID: PMC6430394
DOI/URL:
Notes: Source: Scopus
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MSK Authors
  1. Maria Eugenia Arcila
    350 Arcila
  2. Sean McCarthy Devlin
    305 Devlin
  3. Mikhail Roshal
    68 Roshal
  4. Carl Ola Landgren
    198 Landgren
  5. Caleb   Ho
    23 Ho
  6. Even Holth Rustad
    7 Rustad
  7. Akshar Patel
    8 Patel
  8. Denise Chen
    1 Chen