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dc.contributor.authorStratton, Men_US
dc.date.accessioned2018-06-11T10:46:20Z
dc.date.issued2008-09en_US
dc.identifier35en_US
dc.identifier.citationPROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 pp. 13081 - 13086en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1803
dc.description.abstractDuring the clonal expansion of cancer from an ancestral cell with an initiating oncogenic mutation to symptomatic neoplasm, the occurrence of somatic mutations (both driver and passenger) can be used to track the on-going evolution of the neoplasm. All subclones within a cancer are phylogenetically related, with the prevalence of each subclone determined by its evolutionary fitness and the timing of its origin relative to other subclones. Recently developed massively parallel sequencing platforms promise the ability to detect rare subclones of genetic variants without a priori knowledge of the mutations involved. We used ultra-deep pyro-sequencing to investigate intraclonal diversification at the Ig heavy chain locus in 22 patients with B-cell chronic lymphocytic leukemia. Analysis of a non-polymorphic control locus revealed artifactual insertions and deletions resulting from sequencing errors and base substitutions caused by polymerase misincorporation during PCR amplification. We developed an algorithm to differentiate genuine haplotypes of somatic hypermutations from such artifacts. This proved capable of detecting multiple rare subclones with frequencies as low as 1 in 5000 copies and allowed the characterization of phylogenetic interrelationships among subclones within each patient. This study demonstrates the potential for ultra-deep resequencing to recapitulate the dynamics of clonal evolution in cancer cell populations.en_US
dc.format.extent13081 - 13086en_US
dc.titleSubclonal phylogenetic structures in cancer revealed by ultra-deep sequencingen_US
dc.typeJournal Article
rioxxterms.licenseref.startdate2008-09en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfPROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICAen_US
pubs.noteskeywords: CHRONIC LYMPHOCYTIC-LEUKEMIA; POLYMERASE CHAIN-REACTION; CHRONIC MYELOID-LEUKEMIA; DRUG-RESISTANCE; B-CELLS; INTRACLONAL DIVERSIFICATION; SOMATIC HYPERMUTATION; CHILDHOOD LEUKEMIA; GENE-MUTATIONS; LUNG-CANCERen_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Genetic Susceptibility
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Genetic Susceptibility
pubs.volume105en_US
pubs.embargo.termsNot knownen_US
icr.researchteamGenetic Susceptibilityen_US
dc.contributor.icrauthorStratton, Michaelen_US


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