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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Gawad, Charles Koh, Winston Quake, Stephen R. |
| Description | Author Affiliation: Gawad C ( Division of Pediatric Hematology-Oncology, Department of Pediatrics, Stanford University, Palo Alto, CA 94305); Koh W ( Departments of Bioengineering and Applied Physics, Stanford University and Howard Hughes Medical Institute, Stanford,CA 94305.); Quake SR ( Departments of Bioengineering and Applied Physics, Stanford University and Howard Hughes Medical Institute, Stanford,CA 94305 quake@stanford.edu.); |
| 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. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 50 |
| Volume Number | 111 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2014-12-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Genetic Variation Genomics Precursor Cell Lymphoblastic Leukemia-Lymphoma Genetics Single-Cell Analysis Clone Cells Physiology DNA Mutational Analysis Exome Microfluidic Analytical Techniques Molecular Sequence Data Polymorphism, Single Nucleotide Sequence Analysis, DNA Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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