title: Single-cell exome sequencing and monoclonal evolution of a JAK2-negative myeloproliferative neoplasm.
abstract: 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.
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Hou
authors.forename: Luting
authors.initials: L
authors.lastname: Song
authors.forename: Ping
authors.initials: P
authors.lastname: Zhu
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.forename: Ye
authors.initials: Y
authors.lastname: Tao
authors.forename: Xun
authors.initials: X
authors.lastname: Xu
authors.forename: Fuqiang
authors.initials: F
authors.lastname: Li
authors.forename: Kui
authors.initials: K
authors.lastname: Wu
authors.forename: Jie
authors.initials: J
authors.lastname: Liang
authors.forename: Di
authors.initials: D
authors.lastname: Shao
authors.forename: Hanjie
authors.initials: H
authors.lastname: Wu
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Ye
authors.forename: Chen
authors.initials: C
authors.lastname: Ye
authors.forename: Renhua
authors.initials: R
authors.lastname: Wu
authors.forename: Min
authors.initials: M
authors.lastname: Jian
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Xie
authors.forename: Ruren
authors.initials: R
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Xiaotian
authors.initials: X
authors.lastname: Yao
authors.forename: Hancheng
authors.initials: H
authors.lastname: Zheng
authors.forename: Chang
authors.initials: C
authors.lastname: Yu
authors.forename: Qibin
authors.initials: Q
authors.lastname: Li
authors.forename: Zhuolin
authors.initials: Z
authors.lastname: Gong
authors.forename: Mao
authors.initials: M
authors.lastname: Mao
authors.forename: Xu
authors.initials: X
authors.lastname: Yang
authors.forename: Lin
authors.initials: L
authors.lastname: Yang
authors.forename: Jingxiang
authors.initials: J
authors.lastname: Li
authors.forename: Wen
authors.initials: W
authors.lastname: Wang
authors.forename: Zuhong
authors.initials: Z
authors.lastname: Lu
authors.forename: Ning
authors.initials: N
authors.lastname: Gu
authors.forename: Goodman
authors.initials: G
authors.lastname: Laurie
authors.forename: Lars
authors.initials: L
authors.lastname: Bolund
authors.forename: Karsten
authors.initials: K
authors.lastname: Kristiansen
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Huanming
authors.initials: H
authors.lastname: Yang
authors.forename: Yingrui
authors.initials: Y
authors.lastname: Li
authors.forename: Xiuqing
authors.initials: X
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
mesh_terms: D060965:Clonal Evolution; D059472:Exome; D020869:Gene Expression Profiling; D015894:Genome, Human; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000235:genetics* / Q000473:pathology*; D059010:Single-Cell Analysis / Q000379:methods*; D013920:Thrombocythemia, Essential / Q000235:genetics*
chemical_list: D053614:Janus Kinase 2