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dc.contributor.authorOrlando, G
dc.contributor.authorLaw, PJ
dc.contributor.authorCornish, AJ
dc.contributor.authorDobbins, SE
dc.contributor.authorChubb, D
dc.contributor.authorBroderick, P
dc.contributor.authorLitchfield, K
dc.contributor.authorHariri, F
dc.contributor.authorPastinen, T
dc.contributor.authorOsborne, CS
dc.contributor.authorTaipale, J
dc.contributor.authorHoulston, RS
dc.date.accessioned2018-11-27T12:04:32Z
dc.date.issued2018-10
dc.identifier.citationNature genetics, 2018, 50 (10), pp. 1375 - 1380
dc.identifier.issn1061-4036
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2956
dc.identifier.eissn1546-1718
dc.identifier.doi10.1038/s41588-018-0211-z
dc.description.abstractEfforts are being directed to systematically analyze the non-coding regions of the genome for cancer-driving mutations 1-6 . cis-regulatory elements (CREs) represent a highly enriched subset of the non-coding regions of the genome in which to search for such mutations. Here we use high-throughput chromosome conformation capture techniques (Hi-C) for 19,023 promoter fragments to catalog the regulatory landscape of colorectal cancer in cell lines, mapping CREs and integrating these with whole-genome sequence and expression data from The Cancer Genome Atlas 7,8 . We identify a recurrently mutated CRE interacting with the ETV1 promoter affecting gene expression. ETV1 expression influences cell viability and is associated with patient survival. We further refine our understanding of the regulatory effects of copy-number variations, showing that RASL11A is targeted by a previously identified enhancer amplification 1 . This study reveals new insights into the complex genetic alterations driving tumor development, providing a paradigm for employing chromosome conformation capture to decipher non-coding CREs relevant to cancer biology.
dc.formatPrint-Electronic
dc.format.extent1375 - 1380
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://www.rioxx.net/licenses/under-embargo-all-rights-reserved
dc.subjectCaco-2 Cells
dc.subjectHela Cells
dc.subjectHT29 Cells
dc.subjectK562 Cells
dc.subjectTumor Cells, Cultured
dc.subjectChromosomes, Human
dc.subjectHumans
dc.subjectColorectal Neoplasms
dc.subjectCell Transformation, Neoplastic
dc.subjectDNA, Neoplasm
dc.subjectCodon, Nonsense
dc.subjectComputational Biology
dc.subjectRegulatory Sequences, Nucleic Acid
dc.subjectNucleic Acid Conformation
dc.subjectGene Frequency
dc.subjectDatabases, Genetic
dc.subjectPromoter Regions, Genetic
dc.subjectHep G2 Cells
dc.subjectHigh-Throughput Nucleotide Sequencing
dc.subjectMCF-7 Cells
dc.titlePromoter capture Hi-C-based identification of recurrent noncoding mutations in colorectal cancer.
dc.typeJournal Article
dcterms.dateAccepted2018-07-27
rioxxterms.versionofrecord10.1038/s41588-018-0211-z
rioxxterms.licenseref.urihttps://www.rioxx.net/licenses/under-embargo-all-rights-reserved
rioxxterms.licenseref.startdate2018-10
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfNature genetics
pubs.issue10
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/Genetics and Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Cancer Genomics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Molecular & Population Genetics
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/Genetics and Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Cancer Genomics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Molecular & Population Genetics
pubs.publication-statusPublished
pubs.volume50
pubs.embargo.termsNo embargo
icr.researchteamCancer Genomicsen_US
icr.researchteamMolecular & Population Geneticsen_US
dc.contributor.icrauthorLaw, Philipen
dc.contributor.icrauthorCornish, Alexanderen
dc.contributor.icrauthorBroderick, Peteren
dc.contributor.icrauthorHoulston, Richarden
dc.contributor.icrauthorLitchfield, Kevinen


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