Single-Cell Exome Sequencing and Monoclonal Evolution of a JAK2-Negative Myeloproliferative Neoplasm
نویسندگان
چکیده
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.
منابع مشابه
Prevalence of MPL (W515K/L) Mutations in Patients with Negative-JAK2 (V617F) Myeloproliferative Neoplasm in North-East of Iran
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Fig. S1: Mutation matrices used in this study. (a) JAK2-negative myeloproliferative neoplasm: single-cell exome sequencing of 58 tumor cells, 18 mutation sites selected for importance out of 712 SNVs [1]. Estimated error rates: 0.4309 for allelic dropout and 6.04 × 10−6 for false discovery, 45% missing data points. The mutation matrix is taken from [2]. Color coding of matrix cells: blue hetero...
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عنوان ژورنال:
- Cell
دوره 148 شماره
صفحات -
تاریخ انتشار 2012