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  - 2013/09/20 
JF  - Genome Research 
JO  - Genome Research 
DO  - 10.1101/gr.159913.113 
SP  - gr.159913.113 
UR  - http://genome.cshlp.org/content/early/2013/09/20/gr.159913.113.abstract 
N2  - The development of cancer is a dynamic evolutionary process in which intra-clonal, genetic diversity provides a substrate for clonal selection and a source of therapeutic escape. The complexity and topography of intra-clonal genetic architecture has major implications for biopsy-based prognosis and for targeted therapy. High depth, next generation sequencing (NGS) efficiently captures the mutational load of individual tumours or biopsies.  But, being a snapshot portrait of total DNA, it disguises the fundamental features of sub-clonal 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 leukaemic cells with known mutational spectra as a tractable model.  DNA from flow sorted single cells is screened using multiplex targeted Q-PCR within a micro-fluidic platform allowing unbiased single cell selection, high throughput and comprehensive analysis for all main varieties of genetic abnormalities: chimaeric 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 sub-clonal genetic architectures and phylogenies. 
ER  -