Single-cell Exome Sequencing and Monoclonal Evolution of a JAK2-negative Myeloproliferative Neoplasm

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. Our findings 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. Our work allowed the resolution of the disease-related genetic architecture at the single-cell nucleotide level and the identification of genes potentially involved in myeloproliferative neoplasm progression. Further, we established a single-cell sequencing method, which opens the way for detailed analyses of a variety of tumor types that may be genetically more complex between different patients.