TY  - JOUR
A1  - Wang, Lili
A1  - Fan, Jean
A1  - Francis, Joshua M.
A1  - Georghiou, George
A1  - Hergert, Sarah
A1  - Li, Shuqiang
A1  - Gambe, Rutendo
A1  - Zhou, Chensheng W.
A1  - Yang, Chunxiao
A1  - Xiao, Sheng
A1  - Cin, Paola Dal
A1  - Bowden, Michaela
A1  - Kotliar, Dylan
A1  - Shukla, Sachet A.
A1  - Brown, Jennifer R.
A1  - Neuberg, Donna
A1  - Alessi, Dario R.
A1  - Zhang, Cheng-Zhong
A1  - Kharchenko, Peter V.
A1  - Livak, Kenneth J.
A1  - Wu, Catherine J.
T1  - Integrated single-cell genetic and transcriptional analysis suggests novel drivers of chronic lymphocytic leukemia
Y1  - 2017/08/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 1300 
EP  - 1311 
DO  - 10.1101/gr.217331.116 
VL  - 27 
IS  - 8 
UR  - http://genome.cshlp.org/content/27/8/1300.abstract 
N2  - Intra-tumoral genetic heterogeneity has been characterized across cancers by genome sequencing of bulk tumors, including chronic lymphocytic leukemia (CLL). In order to more accurately identify subclones, define phylogenetic relationships, and probe genotype–phenotype relationships, we developed methods for targeted mutation detection in DNA and RNA isolated from thousands of single cells from five CLL samples. By clearly resolving phylogenic relationships, we uncovered mutated LCP1 and WNK1 as novel CLL drivers, supported by functional evidence demonstrating their impact on CLL pathways. Integrative analysis of somatic mutations with transcriptional states prompts the idea that convergent evolution generates phenotypically similar cells in distinct genetic branches, thus creating a cohesive expression profile in each CLL sample despite the presence of genetic heterogeneity. Our study highlights the potential for single-cell RNA-based targeted analysis to sensitively determine transcriptional and mutational profiles of individual cancer cells, leading to increased understanding of driving events in malignancy. 
ER  -