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dc.contributor.authorYost, Sen_US
dc.contributor.authorde Wolf, Ben_US
dc.contributor.authorHanks, Sen_US
dc.contributor.authorZachariou, Aen_US
dc.contributor.authorMarcozzi, Cen_US
dc.contributor.authorClarke, Men_US
dc.contributor.authorde Voer, Ren_US
dc.contributor.authorEtemad, Ben_US
dc.contributor.authorUijttewaal, Een_US
dc.contributor.authorRamsay, Een_US
dc.contributor.authorWylie, Hen_US
dc.contributor.authorElliott, Aen_US
dc.contributor.authorPicton, Sen_US
dc.contributor.authorSmith, Aen_US
dc.contributor.authorSmithson, Sen_US
dc.contributor.authorSeal, Sen_US
dc.contributor.authorRuark, Een_US
dc.contributor.authorHouge, Gen_US
dc.contributor.authorPines, Jen_US
dc.contributor.authorKops, GJPLen_US
dc.contributor.authorRahman, Nen_US
dc.coverage.spatialUnited Statesen_US
dc.date.accessioned2017-11-01T10:58:14Z
dc.date.issued2017-07en_US
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/28553959en_US
dc.identifier.citationNat Genet, 2017, 49 (7), pp. 1148 - 1151en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/884
dc.identifier.eissn1546-1718en_US
dc.identifier.doi10.1038/ng.3883en_US
dc.description.abstractThrough exome sequencing, we identified six individuals with biallelic loss-of-function mutations in TRIP13. All six developed Wilms tumor. Constitutional mosaic aneuploidies, microcephaly, developmental delay and seizures, which are features of mosaic variegated aneuploidy (MVA) syndrome, were more variably present. Through functional studies, we show that TRIP13-mutant patient cells have no detectable TRIP13 and have substantial impairment of the spindle assembly checkpoint (SAC), leading to a high rate of chromosome missegregation. Accurate segregation, as well as SAC proficiency, is rescued by restoring TRIP13 function. Individuals with biallelic TRIP13 or BUB1B mutations have a high risk of embryonal tumors, and here we show that their cells display severe SAC impairment. MVA due to biallelic CEP57 mutations, or of unknown cause, is not associated with embryonal tumors and cells from these individuals show minimal SAC deficiency. These data provide insights into the complex relationships between aneuploidy and carcinogenesis.en_US
dc.format.extent1148 - 1151en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://www.rioxx.net/licenses/under-embargo-all-rights-reserveden_US
dc.subjectATPases Associated with Diverse Cellular Activitiesen_US
dc.subjectAneuploidyen_US
dc.subjectCarrier Proteinsen_US
dc.subjectCell Cycle Proteinsen_US
dc.subjectChild, Preschoolen_US
dc.subjectChromosome Segregationen_US
dc.subjectDNA, Neoplasmen_US
dc.subjectDevelopmental Disabilitiesen_US
dc.subjectFemaleen_US
dc.subjectGenetic Predisposition to Diseaseen_US
dc.subjectHumansen_US
dc.subjectKidney Neoplasmsen_US
dc.subjectLeukemia, Myeloid, Acuteen_US
dc.subjectM Phase Cell Cycle Checkpointsen_US
dc.subjectMicrocephalyen_US
dc.subjectMicrotubule-Associated Proteinsen_US
dc.subjectMosaicismen_US
dc.subjectMutationen_US
dc.subjectNeoplasms, Multiple Primaryen_US
dc.subjectNuclear Proteinsen_US
dc.subjectOvarian Neoplasmsen_US
dc.subjectProtein-Serine-Threonine Kinasesen_US
dc.subjectRNA Stabilityen_US
dc.subjectSeizuresen_US
dc.subjectSertoli-Leydig Cell Tumoren_US
dc.subjectWilms Tumoren_US
dc.titleBiallelic TRIP13 mutations predispose to Wilms tumor and chromosome missegregation.en_US
dc.typeJournal Article
dcterms.dateAccepted2017-05-01en_US
rioxxterms.funderThe Institute of Cancer Researchen_US
rioxxterms.identifier.projectUnspecifieden_US
rioxxterms.versionofrecord10.1038/ng.3883en_US
rioxxterms.licenseref.startdate2017-07en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfNat Geneten_US
pubs.issue7en_US
pubs.notesNo embargoen_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.publication-statusPublisheden_US
pubs.volume49en_US
pubs.embargo.termsNo embargoen_US
icr.researchteamGenetic Susceptibilityen_US
dc.contributor.icrauthorRahman, Saberaen_US
dc.contributor.icrauthorPines, Jonathonen_US
rioxxterms.funder.project354849bd-c553-4e22-868c-8c503e124155en_US


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