Clonal Architecture of Secondary Acute Myeloid Leukemia Defined by Single-Cell Sequencing

Andrew E.O. Hughes, Vincent Magrini, Ryan Demeter, Christopher A. Miller, Robert Fulton, Lucinda L. Fulton, William C. Eades, Kevin Elliott, Sharon Heath, Peter Westervelt, Li Ding, Don Conrad, Brian S. White, Jin Shao, Daniel C. Link, John F. DiPersio, Elaine R. Mardis, Richard K. Wilson, Timothy J. Ley, Matthew J. WalterTimothy A. Graubert

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Next-generation sequencing has been used to infer the clonality of heterogeneous tumor samples. These analyses yield specific predictions-the population frequency of individual clones, their genetic composition, and their evolutionary relationships-which we set out to test by sequencing individual cells from three subjects diagnosed with secondary acute myeloid leukemia, each of whom had been previously characterized by whole genome sequencing of unfractionated tumor samples. Single-cell mutation profiling strongly supported the clonal architecture implied by the analysis of bulk material. In addition, it resolved the clonal assignment of single nucleotide variants that had been initially ambiguous and identified areas of previously unappreciated complexity. Accordingly, we find that many of the key assumptions underlying the analysis of tumor clonality by deep sequencing of unfractionated material are valid. Furthermore, we illustrate a single-cell sequencing strategy for interrogating the clonal relationships among known variants that is cost-effective, scalable, and adaptable to the analysis of both hematopoietic and solid tumors, or any heterogeneous population of cells.

Original languageEnglish (US)
Article numbere1004462
JournalPLoS genetics
Volume10
Issue number7
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

Fingerprint

myeloid leukemia
Acute Myeloid Leukemia
tumor
neoplasms
Neoplasms
cells
High-Throughput Nucleotide Sequencing
Population
clone
mutation
Nucleotides
genome
Clone Cells
nucleotides
Genome
clones
Costs and Cost Analysis
sampling
Mutation
prediction

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

Cite this

Hughes, A. E. O., Magrini, V., Demeter, R., Miller, C. A., Fulton, R., Fulton, L. L., ... Graubert, T. A. (2014). Clonal Architecture of Secondary Acute Myeloid Leukemia Defined by Single-Cell Sequencing. PLoS genetics, 10(7), [e1004462]. https://doi.org/10.1371/journal.pgen.1004462

Clonal Architecture of Secondary Acute Myeloid Leukemia Defined by Single-Cell Sequencing. / Hughes, Andrew E.O.; Magrini, Vincent; Demeter, Ryan; Miller, Christopher A.; Fulton, Robert; Fulton, Lucinda L.; Eades, William C.; Elliott, Kevin; Heath, Sharon; Westervelt, Peter; Ding, Li; Conrad, Don; White, Brian S.; Shao, Jin; Link, Daniel C.; DiPersio, John F.; Mardis, Elaine R.; Wilson, Richard K.; Ley, Timothy J.; Walter, Matthew J.; Graubert, Timothy A.

In: PLoS genetics, Vol. 10, No. 7, e1004462, 01.01.2014.

Research output: Contribution to journalArticle

Hughes, AEO, Magrini, V, Demeter, R, Miller, CA, Fulton, R, Fulton, LL, Eades, WC, Elliott, K, Heath, S, Westervelt, P, Ding, L, Conrad, D, White, BS, Shao, J, Link, DC, DiPersio, JF, Mardis, ER, Wilson, RK, Ley, TJ, Walter, MJ & Graubert, TA 2014, 'Clonal Architecture of Secondary Acute Myeloid Leukemia Defined by Single-Cell Sequencing', PLoS genetics, vol. 10, no. 7, e1004462. https://doi.org/10.1371/journal.pgen.1004462
Hughes AEO, Magrini V, Demeter R, Miller CA, Fulton R, Fulton LL et al. Clonal Architecture of Secondary Acute Myeloid Leukemia Defined by Single-Cell Sequencing. PLoS genetics. 2014 Jan 1;10(7). e1004462. https://doi.org/10.1371/journal.pgen.1004462
Hughes, Andrew E.O. ; Magrini, Vincent ; Demeter, Ryan ; Miller, Christopher A. ; Fulton, Robert ; Fulton, Lucinda L. ; Eades, William C. ; Elliott, Kevin ; Heath, Sharon ; Westervelt, Peter ; Ding, Li ; Conrad, Don ; White, Brian S. ; Shao, Jin ; Link, Daniel C. ; DiPersio, John F. ; Mardis, Elaine R. ; Wilson, Richard K. ; Ley, Timothy J. ; Walter, Matthew J. ; Graubert, Timothy A. / Clonal Architecture of Secondary Acute Myeloid Leukemia Defined by Single-Cell Sequencing. In: PLoS genetics. 2014 ; Vol. 10, No. 7.
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