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

Content Provider	Semantic Scholar
Author	Gawad, Charles Koh, Winston Quake, Stephen R.
Copyright Year	2014
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 identified clones within the same patient that are arrested at varied stages in B-cell development. Taken together, these data order the sequence of genetic events that underlie childhood ALL and provide a framework for understanding the development of the disease at single-cell resolution.
File Format	PDF HTM / HTML
DOI	10.1073/pnas.1420822111
PubMed reference number	25425670
Journal	Medline
Volume Number	111
Issue Number	50
Alternate Webpage(s)	http://www.pnas.org/content/111/50/17947.full.pdf
Alternate Webpage(s)	https://doi.org/10.1073/pnas.1420822111
Journal	Proceedings of the National Academy of Sciences of the United States of America
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article