RT Journal Article
SR Electronic
T1 High-throughput single-cell DNA sequencing of AML tumors with droplet microfluidics
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 203158
DO 10.1101/203158
A1 Maurizio Pellegrino
A1 Adam Sciambi
A1 Sebastian Treusch
A1 Robert Durruthy-Durruthy
A1 Kaustubh Gokhale
A1 Jose Jacob
A1 Tina X. Chen
A1 William Oldham
A1 Jairo Matthews
A1 Hagop Kantarjian
A1 P. Andrew Futreal
A1 Keyur Patel
A1 Keith W. Jones
A1 Koichi Takahashi
A1 Dennis J. Eastburn
YR 2017
UL http://biorxiv.org/content/early/2017/11/03/203158.abstract
AB 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. Using this approach, we sequenced longitudinally collected 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 tumor cells 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 heterogeneity in AML leading to improved stratification and therapy selection for the disease.