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Cell ; 148(5): 873-85, 2012 Mar 02.
Artículo en Inglés | MEDLINE | ID: mdl-22385957

RESUMEN

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.


Asunto(s)
Evolución Clonal , Perfilación de la Expresión Génica , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Janus Quinasa 2/genética , Trastornos Mieloproliferativos/genética , Trastornos Mieloproliferativos/patología , Análisis de la Célula Individual/métodos , Trombocitemia Esencial/genética , Exoma , Genoma Humano , Humanos , Masculino , Persona de Mediana Edad , Mutación
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