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dc.contributor.authorBaker, A-M
dc.contributor.authorHuang, W
dc.contributor.authorWang, X-MM
dc.contributor.authorJansen, M
dc.contributor.authorMa, X-J
dc.contributor.authorKim, J
dc.contributor.authorAnderson, CM
dc.contributor.authorWu, X
dc.contributor.authorPan, L
dc.contributor.authorSu, N
dc.contributor.authorLuo, Y
dc.contributor.authorDomingo, E
dc.contributor.authorHeide, T
dc.contributor.authorSottoriva, A
dc.contributor.authorLewis, A
dc.contributor.authorBeggs, AD
dc.contributor.authorWright, NA
dc.contributor.authorRodriguez-Justo, M
dc.contributor.authorPark, E
dc.contributor.authorTomlinson, I
dc.contributor.authorGraham, TA
dc.date.accessioned2018-03-26T08:39:21Z
dc.date.issued2017-12-08
dc.identifier.citationNature communications, 2017, 8 (1), pp. 1998 - ?
dc.identifier.issn2041-1723
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1605
dc.identifier.eissn2041-1723
dc.identifier.doi10.1038/s41467-017-02295-5
dc.description.abstractIntra-tumor heterogeneity (ITH) is a major underlying cause of therapy resistance and disease recurrence, and is a read-out of tumor growth. Current genetic ITH analysis methods do not preserve spatial context and may not detect rare subclones. Here, we address these shortfalls by developing and validating BaseScope-a novel mutation-specific RNA in situ hybridization assay. We target common point mutations in the BRAF, KRAS and PIK3CA oncogenes in archival colorectal cancer samples to precisely map the spatial and morphological context of mutant subclones. Computational modeling suggests that subclones must arise sufficiently early, or carry a considerable fitness advantage, to form large or spatially disparate subclones. Examples of putative treatment-resistant cells isolated in small topographical areas are observed. The BaseScope assay represents a significant technical advance for in situ mutation detection that provides new insight into tumor evolution, and could have ramifications for selecting patients for treatment.
dc.formatElectronic
dc.format.extent1998 - ?
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectCell Line, Tumor
dc.subjectHumans
dc.subjectColorectal Neoplasms
dc.subjectNeoplasm Recurrence, Local
dc.subjectProto-Oncogene Proteins B-raf
dc.subjectRNA
dc.subjectIn Situ Hybridization
dc.subjectDNA Mutational Analysis
dc.subjectDrug Resistance, Neoplasm
dc.subjectPoint Mutation
dc.subjectComputer Simulation
dc.subjectProto-Oncogene Proteins p21(ras)
dc.subjectClass I Phosphatidylinositol 3-Kinases
dc.subjectClonal Evolution
dc.titleRobust RNA-based in situ mutation detection delineates colorectal cancer subclonal evolution.
dc.typeJournal Article
dcterms.dateAccepted2017-11-17
rioxxterms.versionofrecord10.1038/s41467-017-02295-5
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2017-12-08
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfNature communications
pubs.issue1
pubs.notesNo embargo
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/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Evolutionary Genomics & Modelling
pubs.organisational-group/ICR/Students
pubs.organisational-group/ICR/Students/PhD and MPhil
pubs.organisational-group/ICR/Students/PhD and MPhil/16/17 Starting Cohort
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/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Evolutionary Genomics & Modelling
pubs.organisational-group/ICR/Students
pubs.organisational-group/ICR/Students/PhD and MPhil
pubs.organisational-group/ICR/Students/PhD and MPhil/16/17 Starting Cohort
pubs.publication-statusPublished
pubs.volume8
pubs.embargo.termsNo embargo
icr.researchteamEvolutionary Genomics & Modellingen_US
dc.contributor.icrauthorHeide, Timonen
dc.contributor.icrauthorSottoriva, Andreaen


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