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

• DOI: 10.1101/gr.232272.117
• Publication Date: 2018-08-07T15:35:12Z
• Authors: Maurizio Pellegrino; Adam Sciambi; Sebastian Treusch; Robert Durruthy-D...; Kaustubh Gokhale; Jose Jacob; Tina X. Chen; Jennifer A. Geis; William Oldham; Jairo Matthews; Hagop Kantarjian; P. Andrew Futreal; Keyur Patel; Keith W. Jones; Koichi Takahashi; Dennis J. Eastburn
• Keywords: Single cell sequencing

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