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Determination of complex subclonal structures of hematological malignancies by multiplexed genotyping of blood progenitor colonies.

Published version
Peer-reviewed

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Authors

Nice, Francesca L 
Massie, Charlie E 
Klampfl, Thorsten 
Green, Anthony R 

Abstract

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.

Description

Keywords

Alleles, Clone Cells, Cluster Analysis, DNA Mutational Analysis, DNA, Neoplasm, Erythroid Precursor Cells, Genotyping Techniques, Granulocytes, Hematologic Neoplasms, High-Throughput Nucleotide Sequencing, Humans, Janus Kinase 2, Mutation, Mutation, Missense, Polycythemia Vera, Polymorphism, Single Nucleotide, Sequence Analysis, DNA

Journal Title

Exp Hematol

Conference Name

Journal ISSN

0301-472X
1873-2399

Volume Title

57

Publisher

Elsevier BV
Sponsorship
Medical Research Council (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)
Leukemia & Lymphoma Society (7001-12)
Leukaemia & Lymphoma Research (13003)
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)