| Autor: |
Velten, Lars, Story, Benjamin A., Hernandez-Malmierca, Pablo, Milbank, Jennifer, Paulsen, Malte, Lutz, Christoph, Nowak, Daniel, Jann, Johann-Christoph, Pabst, Caroline, Boch, Tobias, Hofmann, Wolf-Karsten, Mueller-Tidow, Carsten, Raffel, Simon, Trumpp, Andreas, Haas, Simon, Steinmetz, Lars M |
| Jazyk: |
angličtina |
| Rok vydání: |
2018 |
| DOI: |
10.1101/500108 |
| Popis: |
The step-wise acquisition of genetic abnormalities in cancer is thought to represent a major driver of disease initiation, relapse and therapy resistance. Acute myeloid leukemia (AML) represents a prime example of an aggressive cancer that develops in a multi-step manner from multipotent hematopoietic progenitors via pre-leukemic intermediates to leukemic cells. While bulk and single-cell genomics provide powerful tools to study the phylogenetics of cancer evolution, the specific transcriptomic changes induced by the accumulation of mutations remain largely unexplored. Here, we introduce MutaSeq, a combined single-cell genetic and transcriptomics platform for the identification of molecular consequences of cancer evolution. Through in-depth profiling of an AML patient, we demonstrate that MutaSeq is capable of: (1) fine-mapping clonal and developmental hierarchies (2) quantifying the ability of leukemic and pre-leukemic clones to give rise to mature lineages and (3) identifying surface markers and mRNA transcripts specific to pre-leukemic, leukemic, and residual healthy cells. The experimental and analytical approach presented here is broadly applicable to other types of cancer, and can help identify targets for eradicating both pre-cancerous and cancerous reservoirs of relapse. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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