Genome-wide Segregation of Single Nucleotide and Structural Variants into Single Leukemia Cells

Abstract

We present a new approach for determining comprehensive variant profiles of single cells using a microfluidic amplicon-based strategy. This method can be used to reconstruct the clonal architecture and mutational history of a malignancy using all classes and sizes of single nucleotide and structural variants, providing insights into the temporal changes in mutational classes and processes that led to the development of a cancer. Using this approach, we interrogated single cells from a patient with leukemia, determining that processes producing structural variation preceded single nucleotides changes in the development of that malignancy.