Determination of complex subclonal structures of hematological malignancies by multiplexed genotyping of blood progenitor colonies.
Publication Date
2018-01Journal Title
Experimental hematology
ISSN
0301-472X
Publisher
Elsevier
Volume
57
Pages
60-64.e1
Language
eng
Type
Article
This Version
VoR
Physical Medium
Print-Electronic
Metadata
Show full item recordCitation
Nice, F., Massie, C., Klampfl, T., & Green, T. (2018). Determination of complex subclonal structures of hematological malignancies by multiplexed genotyping of blood progenitor colonies.. Experimental hematology, 57 60-64.e1. https://doi.org/10.1016/j.exphem.2017.09.011
Abstract
Current next generation sequencing (NGS) technologies allow unprecedented insights into the mutational profiles of tumours. 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 (BFU-E) colonies based on NGS results to assess subclonal tumour 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.
Keywords
Granulocytes, Clone Cells, Humans, Hematologic Neoplasms, Polycythemia Vera, DNA, Neoplasm, Cluster Analysis, Sequence Analysis, DNA, DNA Mutational Analysis, Mutation, Mutation, Missense, Polymorphism, Single Nucleotide, Alleles, Janus Kinase 2, Erythroid Precursor Cells, High-Throughput Nucleotide Sequencing, Genotyping Techniques
Sponsorship
Work in ARG lab has been supported by the Leukemia and Lymphoma Society (grant 7001-12), the National Institute of Health Research (grant NF-SI-0512-10079) and core support grants by the MRC and Wellcome Trust to the Cambridge Institute for Medical Research (100140/Z/12/Z) and Wellcome Trust-MRC Cambridge Stem Cell Institute (097922/Z/11/Z). Work in ARG's laboratory has in addition been supported by Cancer Research UK (grants C1163/A12765 and C1163/A21762), Bloodwise (grant 13003) and the Wellcome Trust (grant 104710/Z/14/Z)
Funder references
MRC (MC_PC_12009)
Wellcome Trust (100140/Z/12/Z)
Wellcome Trust (097922/Z/11/Z)
WELLCOME TRUST (104710/Z/14/Z)
Cancer Research UK (21762)
Embargo Lift Date
2100-01-01
Identifiers
External DOI: https://doi.org/10.1016/j.exphem.2017.09.011
This record's URL: https://www.repository.cam.ac.uk/handle/1810/276067
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