Dissecting the clonal origins of childhood acute lymphoblastic leukemia by single-cell genomics.

ABSTRACT: Many cancers have substantial genomic heterogeneity within a given tumor, and to fully understand that diversity requires the ability to perform single cell analysis. We performed targeted sequencing of a panel of single nucleotide variants (SNVs), deletions, and IgH sequences in 1,479 single tumor cells from six acute lymphoblastic leukemia (ALL) patients. By accurately segregating groups of cooccurring mutations into distinct clonal populations, we identified codominant clones in the majority of patients. Evaluation of intraclonal mutation patterns identified clone-specific punctuated cytosine mutagenesis events, showed that most structural variants are acquired before SNVs, determined that KRAS mutations occur late in disease development but are not sufficient for clonal dominance, and

SUBMITTER: Gawad C 

PROVIDER: S-EPMC4273416 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature