This section shows a summary for the selected study (COSU identifier) or publication (COSP identifier). Studies may have been performed by the Sanger Institute Cancer Genome Project, or imported from the ICGC/TCGA. You can see more information on the help pages.
- Dissecting the clonal origins of childhood acute lymphoblastic leukemia by single-cell genomics.
- Paper ID
- Division of Pediatric Hematology-Oncology, Department of Pediatrics, Stanford University, Palo Alto, CA 94305; and Departments of Bioengineering and Applied Physics, Stanford University and Howard Hughes Medical Institute, Stanford,CA 94305.
Proceedings of the National Academy of Sciences of the United States of America, 2014;111(50):17947-52
PMID: 25425670 (view at PubMed or Europe PMC)
- 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.
- Paper Status