Journal
CELL
Volume 148, Issue 5, Pages 873-885Publisher
CELL PRESS
DOI: 10.1016/j.cell.2012.02.028
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Funding
- National Basic Research Program of China (973 program) [2011CB809202, 2011CB809203]
- Chinese 863 program [2009AA022707, 2012AA02A201]
- Shenzhen Municipal Government of China [ZYC201005250020A]
- Key Laboratory Project, Shenzhen City [CX B200903110066A, CXB201108250096A]
- Shenzhen Key Laboratory of Gene Bank for National Life Science
- Innovative Research Team of Guangdong
- Guangdong Enterprise Key Laboratory of Human Disease Genomics
- Danish Natural Science Research Council
- Danish National Research Foundation
- National Natural Science Foundation of China
- Shenzhen Municipal Government
- Local Government of Yantian District of Shenzhen
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Tumor heterogeneity presents a challenge for inferring clonal evolution and driver gene identification. Here, we describe a method for analyzing the cancer genome at a single-cell nucleotide level. To perform our analyses, we first devised and validated a high-throughput whole-genome single-cell sequencing method using two lymphoblastoid cell line single cells. We then carried out whole-exome single-cell sequencing of 90 cells from a JAK2-negative myeloproliferative neoplasm patient. The sequencing data from 58 cells passed our quality control criteria, and these data indicated that this neoplasm represented a monoclonal evolution. We further identified essential thrombocythemia (ET)-related candidate mutations such as SESN2 and NTRK1, which may be involved in neoplasm progression. This pilot study allowed the initial characterization of the disease-related genetic architecture at the single-cell nucleotide level. Further, we established a single-cell sequencing method that opens the way for detailed analyses of a variety of tumor types, including those with high genetic complex between patients.
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