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dc.contributor.authorLitchfield, Ken_US
dc.contributor.authorLevy, Men_US
dc.contributor.authorDudakia, Den_US
dc.contributor.authorProszek, Pen_US
dc.contributor.authorShipley, Cen_US
dc.contributor.authorBasten, Sen_US
dc.contributor.authorRapley, Een_US
dc.contributor.authorBishop, DTen_US
dc.contributor.authorReid, Aen_US
dc.contributor.authorHuddart, Ren_US
dc.contributor.authorBroderick, Pen_US
dc.contributor.authorCastro, DGDen_US
dc.contributor.authorO'Connor, Sen_US
dc.contributor.authorGiles, RHen_US
dc.contributor.authorHoulston, RSen_US
dc.contributor.authorTurnbull, Cen_US
dc.coverage.spatialEnglanden_US
dc.date.accessioned2017-01-09T15:10:11Z
dc.date.issued2016-12-20en_US
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/27996046en_US
dc.identifierncomms13840en_US
dc.identifier.citationNat Commun, 2016, 7 pp. 13840 - ?en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/380
dc.identifier.eissn2041-1723en_US
dc.identifier.doi10.1038/ncomms13840en_US
dc.description.abstractTesticular germ cell tumour (TGCT) is the most common cancer in young men. Here we sought to identify risk factors for TGCT by performing whole-exome sequencing on 328 TGCT cases from 153 families, 634 sporadic TGCT cases and 1,644 controls. We search for genes that are recurrently affected by rare variants (minor allele frequency <0.01) with potentially damaging effects and evidence of segregation in families. A total of 8.7% of TGCT families carry rare disruptive mutations in the cilia-microtubule genes (CMG) as compared with 0.5% of controls (P=2.1 × 10-8). The most significantly mutated CMG is DNAAF1 with biallelic inactivation and loss of DNAAF1 expression shown in tumours from carriers. DNAAF1 mutation as a cause of TGCT is supported by a dnaaf1hu255h(+/-) zebrafish model, which has a 94% risk of TGCT. Our data implicate cilia-microtubule inactivation as a cause of TGCT and provide evidence for CMGs as cancer susceptibility genes.en_US
dc.format.extent13840 - ?en_US
dc.languageengen_US
dc.language.isoengen_US
dc.subjectAnimalsen_US
dc.subjectCiliaen_US
dc.subjectDisease Models, Animalen_US
dc.subjectFemaleen_US
dc.subjectGenetic Predisposition to Diseaseen_US
dc.subjectHumansen_US
dc.subjectLoss of Heterozygosityen_US
dc.subjectMaleen_US
dc.subjectMicrotubule-Associated Proteinsen_US
dc.subjectMiddle Ageden_US
dc.subjectMutationen_US
dc.subjectNeoplasms, Germ Cell and Embryonalen_US
dc.subjectPedigreeen_US
dc.subjectRisk Factorsen_US
dc.subjectTesticular Neoplasmsen_US
dc.subjectWhole Exome Sequencingen_US
dc.subjectZebrafishen_US
dc.titleRare disruptive mutations in ciliary function genes contribute to testicular cancer susceptibility.en_US
dc.typeJournal Article
dcterms.dateAccepted2016-11-04en_US
rioxxterms.versionofrecord10.1038/ncomms13840en_US
rioxxterms.licenseref.startdate2016-12-20en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfNat Communen_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/Genetics and Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Molecular & Population Genetics
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/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Clinical Academic Radiotherapy (Huddart)
pubs.publication-statusPublished onlineen_US
pubs.volume7en_US
pubs.embargo.termsNo embargoen_US
icr.researchteamMolecular & Population Geneticsen_US
icr.researchteamClinical Academic Radiotherapy (Huddart)en_US
dc.contributor.icrauthorHoulston, Richarden_US
dc.contributor.icrauthorHuddart, Roberten_US
dc.contributor.icrauthorBroderick, Peteren_US
dc.contributor.icrauthorLitchfield, Kevinen_US


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