dc.contributor.author | Litchfield, K | |
dc.contributor.author | Levy, M | |
dc.contributor.author | Dudakia, D | |
dc.contributor.author | Proszek, P | |
dc.contributor.author | Shipley, C | |
dc.contributor.author | Basten, S | |
dc.contributor.author | Rapley, E | |
dc.contributor.author | Bishop, DT | |
dc.contributor.author | Reid, A | |
dc.contributor.author | Huddart, R | |
dc.contributor.author | Broderick, P | |
dc.contributor.author | Castro, DGD | |
dc.contributor.author | O'Connor, S | |
dc.contributor.author | Giles, RH | |
dc.contributor.author | Houlston, RS | |
dc.contributor.author | Turnbull, C | |
dc.date.accessioned | 2017-01-09T15:10:11Z | |
dc.date.issued | 2016-12-20 | |
dc.identifier.citation | Nature communications, 2016, 7 pp. 13840 - ? | |
dc.identifier.issn | 2041-1723 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/380 | |
dc.identifier.eissn | 2041-1723 | |
dc.identifier.doi | 10.1038/ncomms13840 | |
dc.description.abstract | Testicular 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. | |
dc.format | Electronic | |
dc.format.extent | 13840 - ? | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | NATURE PUBLISHING GROUP | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Cilia | |
dc.subject | Animals | |
dc.subject | Zebrafish | |
dc.subject | Humans | |
dc.subject | Neoplasms, Germ Cell and Embryonal | |
dc.subject | Testicular Neoplasms | |
dc.subject | Disease Models, Animal | |
dc.subject | Genetic Predisposition to Disease | |
dc.subject | Microtubule-Associated Proteins | |
dc.subject | Risk Factors | |
dc.subject | Pedigree | |
dc.subject | Mutation | |
dc.subject | Loss of Heterozygosity | |
dc.subject | Middle Aged | |
dc.subject | Female | |
dc.subject | Male | |
dc.subject | Whole Exome Sequencing | |
dc.title | Rare disruptive mutations in ciliary function genes contribute to testicular cancer susceptibility. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2016-11-04 | |
rioxxterms.versionofrecord | 10.1038/ncomms13840 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2016-12-20 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Nature communications | |
pubs.notes | No 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/Primary Group/ICR Divisions/Radiotherapy and Imaging | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Clinical Academic Radiotherapy (Huddart) | |
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/Primary Group/ICR Divisions/Radiotherapy and Imaging | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Clinical Academic Radiotherapy (Huddart) | |
pubs.publication-status | Published | |
pubs.volume | 7 | |
pubs.embargo.terms | No embargo | |
icr.researchteam | Cancer Genomics | |
icr.researchteam | Molecular & Population Genetics | |
icr.researchteam | Clinical Academic Radiotherapy (Huddart) | |
dc.contributor.icrauthor | Litchfield, Kevin | |
dc.contributor.icrauthor | Huddart, Robert | |
dc.contributor.icrauthor | Broderick, Peter | |
dc.contributor.icrauthor | Houlston, Richard | |
dc.contributor.icrauthor | Turnbull, Clare | |