title: Single-cell sequencing and tumorigenesis: improved understanding of tumor evolution and metastasis.
abstract: Extensive genomic and transcriptomic heterogeneity in human cancer often negatively impacts treatment efficacy and survival, thus posing a significant ongoing challenge for modern treatment regimens. State-of-the-art DNA- and RNA-sequencing methods now provide high-resolution genomic and gene expression portraits of individual cells, facilitating the study of complex molecular heterogeneity in cancer. Important developments in single-cell sequencing (SCS) technologies over the past 5 years provide numerous advantages over traditional sequencing methods for understanding the complexity of carcinogenesis, but significant hurdles must be overcome before SCS can be clinically useful. In this review, we: (1) highlight current methodologies and recent technological advances for isolating single cells, single-cell whole-genome and whole-transcriptome amplification using minute amounts of nucleic acids, and SCS, (2) summarize research investigating molecular heterogeneity at the genomic and transcriptomic levels and how this heterogeneity affects clonal evolution and metastasis, and (3) discuss the promise for integrating SCS in the clinical care arena for improved patient care.
authors.affiliation: Chan Soon-Shiong Institute of Molecular Medicine at Windber, 620 Seventh Street, Windber, PA, 15963, USA.
authors.forename: Darrell L
authors.initials: DL
authors.lastname: Ellsworth
authors.affiliation: Chan Soon-Shiong Institute of Molecular Medicine at Windber, 620 Seventh Street, Windber, PA, 15963, USA.
authors.forename: Heather L
authors.initials: HL
authors.lastname: Blackburn
authors.affiliation: Murtha Cancer Center, Walter Reed National Military Medical Center, 8901 Rockville Pike, Bethesda, MD, 20889, USA.
authors.forename: Craig D
authors.initials: CD
authors.lastname: Shriver
authors.affiliation: NantWorks, 9920 Jefferson Boulevard, Culver City, CA, 90230, USA.
authors.forename: Shahrooz
authors.initials: S
authors.lastname: Rabizadeh
authors.affiliation: NantWorks, 9920 Jefferson Boulevard, Culver City, CA, 90230, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Soon-Shiong
authors.affiliation: Murtha Cancer Center, 620 Seventh Street, Windber, PA, 15963, USA. r.ellsworth@wriwindber.org.
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Ellsworth
keywords: Cancer; Cancer stem cells; Circulating tumor cells; Single-cell sequencing; Tumor heterogeneity; Whole-genome amplification