High-throughput single-cell DNA sequencing of acute myeloid leukemia tumors with droplet microfluidics | Zendy

Maurizio Pellegrino | Zendy; Adam Sciambi | Zendy; Sebastian Treusch | Zendy; Robert Durruthy-Durruthy | Zendy; Kaustubh Gokhale | Zendy; Jose Jacob | Zendy; Tina X. Chen | Zendy; Jennifer A. Geis | Zendy; William M. Oldham | Zendy; Jairo Matthews | Zendy; Hagop M. Kantarjian | Zendy; P. Andrew Futreal | Zendy; Keyur P. Patel | Zendy; Keith Jones | Zendy; Koichi Takahashi | Zendy; Dennis J. Eastburn | Zendy

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High-throughput single-cell DNA sequencing of acute myeloid leukemia tumors with droplet microfluidics

Author(s) -

Maurizio Pellegrino,

Adam Sciambi,

Sebastian Treusch,

Robert Durruthy-Durruthy,

Kaustubh Gokhale,

Jose Jacob,

Tina X. Chen,

Jennifer A. Geis,

William M. Oldham,

Jairo Matthews,

Hagop M. Kantarjian,

P. Andrew Futreal,

Keyur P. Patel,

Keith Jones,

Koichi Takahashi,

Dennis J. Eastburn

Publication year - 2018

Publication title -

genome research

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 9.556

H-Index - 297

eISSN - 1549-5469

pISSN - 1088-9051

DOI - 10.1101/gr.232272.117

Subject(s) - biology , myeloid leukemia , dna sequencing , somatic evolution in cancer , myeloid , computational biology , single cell sequencing , genetics , deep sequencing , genetic heterogeneity , microfluidics , dna , cancer , exome sequencing , mutation , gene , cancer research , genome , phenotype , materials science , nanotechnology

To enable the characterization of genetic heterogeneity in tumor cell populations, we developed a novel microfluidic approach that barcodes amplified genomic DNA from thousands of individual cancer cells confined to droplets. The barcodes are then used to reassemble the genetic profiles of cells from next-generation sequencing data. By using this approach, we sequenced longitudinally collected acute myeloid leukemia (AML) tumor populations from two patients and genotyped up to 62 disease relevant loci across more than 16,000 individual cells. Targeted single-cell sequencing was able to sensitively identify cells harboring pathogenic mutations during complete remission and uncovered complex clonal evolution within AML tumors that was not observable with bulk sequencing. We anticipate that this approach will make feasible the routine analysis of AML heterogeneity, leading to improved stratification and therapy selection for the disease.

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