TY  - JOUR
A1  - Potter, Nicola E.
A1  - Ermini, Luca
A1  - Papaemmanuil, Elli
A1  - Cazzaniga, Giovanni
A1  - Vijayaraghavan, Gowri
A1  - Titley, Ian
A1  - Ford, Anthony
A1  - Campbell, Peter
A1  - Kearney, Lyndal
A1  - Greaves, Mel
T1  - Single-cell mutational profiling and clonal phylogeny in cancer
Y1  - 2013/12/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 2115 
EP  - 2125 
DO  - 10.1101/gr.159913.113 
VL  - 23 
IS  - 12 
UR  - http://genome.cshlp.org/content/23/12/2115.abstract 
N2  - The development of cancer is a dynamic evolutionary process in which intraclonal, genetic diversity provides a substrate for clonal selection and a source of therapeutic escape. The complexity and topography of intraclonal genetic architectures have major implications for biopsy-based prognosis and for targeted therapy. High-depth, next-generation sequencing (NGS) efficiently captures the mutational load of individual tumors or biopsies. But, being a snapshot portrait of total DNA, it disguises the fundamental features of subclonal variegation of genetic lesions and of clonal phylogeny. Single-cell genetic profiling provides a potential resolution to this problem, but methods developed to date all have limitations. We present a novel solution to this challenge using leukemic cells with known mutational spectra as a tractable model. DNA from flow-sorted single cells is screened using multiplex targeted Q-PCR within a microfluidic platform allowing unbiased single-cell selection, high-throughput, and comprehensive analysis for all main varieties of genetic abnormalities: chimeric gene fusions, copy number alterations, and single-nucleotide variants. We show, in this proof-of-principle study, that the method has a low error rate and can provide detailed subclonal genetic architectures and phylogenies. 
ER  -