Determination of complex subclonal structures of hematological malignancies by multiplexed genotyping of blood progenitor colonies
| Autor: | Nice, Francesca L, Massie, Charlie E, Klampfl, Thorsten, Green, Anthony R |
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| Přispěvatelé: | Massie, Charles [0000-0003-2314-4843], Green, Tony [0000-0002-9795-0218], Apollo - University of Cambridge Repository |
| Rok vydání: | 2018 |
| Předmět: |
Erythroid Precursor Cells
Genotyping Techniques DNA Mutational Analysis Mutation Missense High-Throughput Nucleotide Sequencing DNA Neoplasm Sequence Analysis DNA Janus Kinase 2 Polymorphism Single Nucleotide Article Clone Cells Hematologic Neoplasms Mutation Cluster Analysis Humans Polycythemia Vera health care economics and organizations Alleles Granulocytes |
| Zdroj: | Experimental Hematology |
| Popis: | Highlights • Complex clonal hierarchies are difficult to predict computationally from NGS data. • Multiplexed genotyping of BFU-Es based on NGS data allowed for the determination of a complex subclonal composition in a patient with MPN. • Analysis of subclonal composition allowed for the determination of the order of acquisition of mutations. Current next-generation sequencing (NGS) technologies allow unprecedented insights into the mutational profiles of tumors. Recent studies in myeloproliferative neoplasms have further demonstrated that, not only the mutational profile, but also the order in which these mutations are acquired is relevant for our understanding of the disease. Our ability to assign mutation order from NGS data alone is, however, limited. Here, we present a strategy of highly multiplexed genotyping of burst forming unit-erythroid colonies based on NGS results to assess subclonal tumor structure. This allowed for the generation of complex clonal hierarchies and determination of order of mutation acquisition far more accurately than was possible from NGS data alone. |
| Databáze: | OpenAIRE |
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