TY - JOUR A1 - Pellegrino, Maurizio A1 - Sciambi, Adam A1 - Treusch, Sebastian A1 - Durruthy-Durruthy, Robert A1 - Gokhale, Kaustubh A1 - Jacob, Jose A1 - Chen, Tina X. A1 - Geis, Jennifer A. A1 - Oldham, William A1 - Matthews, Jairo A1 - Kantarjian, Hagop A1 - Futreal, P. Andrew A1 - Patel, Keyur A1 - Jones, Keith W. A1 - Takahashi, Koichi A1 - Eastburn, Dennis J. T1 - High-throughput single-cell DNA sequencing of acute myeloid leukemia tumors with droplet microfluidics Y1 - 2018/09/01 JF - Genome Research JO - Genome Research SP - 1345 EP - 1352 DO - 10.1101/gr.232272.117 VL - 28 IS - 9 UR - http://genome.cshlp.org/content/28/9/1345.abstract N2 - 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. ER -