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| Status |
Public on Sep 08, 2020 |
| Title |
Clonal Evolution of Acute Myeloid Leukemia Revealed by High-Throughput Single-Cell Genomics |
| Organism |
Homo sapiens |
| Experiment type |
Genome variation profiling by SNP array
SNP genotyping by SNP array
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| Summary |
Clonal diversity contributes to treatment resistance and cancer recurrence. Precise delineation of clonal substructure is essential to understand the resistance mechanism, however, bulk DNA sequencing cannot accurately resolve the complex clonal architectures. Here we report the single-cell DNA sequencing of 123 acute myeloid leukemia (AML) patients and provide cell-level evidence of co-occurrence and mutual exclusivity among driver mutations. Reconstruction of tumor phylogeny uncovers linear and branching clonal evolution patterns, with the latter involving functional convergence. Single-cell DNA sequencing of xenotransplanted samples reveales clonal diversity in leukemia initiating cell populations. Simultaneous single-cell profiling of mutations and cell surface proteins provides cellular genotype-phenotype associations. Analysis of longitudinal samples visualizes the behavior of each individual clone in response to therapy, illustrating the underlying evolutionary process of therapeutic resistance and disease recurrence. Together, these data portray clonal diversity, architecture, and evolution of AML, and highlight their clinical relevance in the era of precision medicine.
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| Overall design |
Genomic DNA from 40 samples in which scDNA-seq data showed at least 5% of homozygously mutated clones were analyzed.
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| Contributor(s) |
Morita K, Wang F, Jahn K, Hu T, Tanaka T, Sasaki Y, Kuipers J, Loghavi S, Wang SA, Yan Y, Furudate K, Matthews J, Little L, Gumbs C, Zhang J, Song X, Thompson E, Patel KP, Bueso-Ramos CE, DiNardo CD, Ravandi F, Jabbour E, Andreeff M, Cortes J, Bhalla K, Garcia-Manero G, Kantarjian H, Konopleva M, Nakada D, Navin N, Beerenwinkel N, Futreal PA, Takahashi K |
| Citation(s) |
33087716 |
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| Submission date |
Aug 26, 2020 |
| Last update date |
Dec 08, 2020 |
| Contact name |
FENG WANG |
| E-mail(s) |
FWang6@mdanderson.org
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| Organization name |
UT MD Anderson Cancer Center
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| Street address |
1881 East Road
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| City |
Houston |
| State/province |
TX |
| ZIP/Postal code |
77054 |
| Country |
USA |
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| Platforms (1) |
| GPL16110 |
Illumina HumanOmni2.5 BeadChip (hg19) |
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| Samples (40)
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| Relations |
| BioProject |
PRJNA659536 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE156934_Batch1.matrix.BAF.GEO.ID.txt.gz |
86.2 Mb |
(ftp)(http) |
TXT |
| GSE156934_Batch1.matrix.LRR.GEO.ID.txt.gz |
106.4 Mb |
(ftp)(http) |
TXT |
| GSE156934_Batch2.matrix.BAF.GEO.ID.txt.gz |
77.5 Mb |
(ftp)(http) |
TXT |
| GSE156934_Batch2.matrix.LRR.GEO.ID.txt.gz |
93.6 Mb |
(ftp)(http) |
TXT |
| GSE156934_Batch3.matrix.BAF.GEO.ID.txt.gz |
71.6 Mb |
(ftp)(http) |
TXT |
| GSE156934_Batch3.matrix.LRR.GEO.ID.txt.gz |
89.3 Mb |
(ftp)(http) |
TXT |
| GSE156934_RAW.tar |
1.3 Gb |
(http)(custom) |
TAR (of IDAT) |
| Processed data are available on Series record |
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