Unravelling Intratumoral Heterogeneity through High-Sensitivity Single-Cell Mutational Analysis and Parallel RNA Sequencing

• DOI: 10.1016/j.molcel.2019.01.009
• Publication Date: 2019-02-12T03:55:40Z
• Authors: Alba Rodriguez-Meira; Gemma Buck; Sally-Ann Clark; Benjamin J. Povin...; Veronica Alcolea; Eleni Louka; Simon McGowan; Angela Hamblin; Nikolaos Sousos; Nikolaos Barkas; Alice Giustacchini; Bethan Psaila; Sten Eirik W. Jac...; Supat Thongjuea; Adam J. Mead
• Keywords: Single-Cell Analysis; Single cell sequencing; RNA-Seq

Single-cell RNA sequencing (scRNA-seq) has emerged as a powerful tool for resolving transcriptional heterogeneity. However, its application to studying cancerous tissues is currently hampered by the lack of coverage across key mutation hotspots in vast majority cells; this prevents correlation genetic and readouts from same single cell. To overcome this, we developed TARGET-seq, method high-sensitivity detection multiple mutations within cells both genomic coding DNA, parallel with unbiased whole-transcriptome analysis. Applying TARGET-seq 4,559 cells, demonstrate how technique uniquely resolves tumor heterogeneity myeloproliferative neoplasms (MPN) stem progenitor providing insights into deregulated pathways mutant non-mutant cells. molecular signatures genetically distinct subclones cancer