dc.contributor.author | Litchfield, K | |
dc.contributor.author | Levy, M | |
dc.contributor.author | Orlando, G | |
dc.contributor.author | Loveday, C | |
dc.contributor.author | Law, PJ | |
dc.contributor.author | Migliorini, G | |
dc.contributor.author | Holroyd, A | |
dc.contributor.author | Broderick, P | |
dc.contributor.author | Karlsson, R | |
dc.contributor.author | Haugen, TB | |
dc.contributor.author | Kristiansen, W | |
dc.contributor.author | Nsengimana, J | |
dc.contributor.author | Fenwick, K | |
dc.contributor.author | Assiotis, I | |
dc.contributor.author | Kote-Jarai, Z | |
dc.contributor.author | Dunning, AM | |
dc.contributor.author | Muir, K | |
dc.contributor.author | Peto, J | |
dc.contributor.author | Eeles, R | |
dc.contributor.author | Easton, DF | |
dc.contributor.author | Dudakia, D | |
dc.contributor.author | Orr, N | |
dc.contributor.author | Pashayan, N | |
dc.contributor.author | UK Testicular Cancer Collaboration, | |
dc.contributor.author | PRACTICAL Consortium, | |
dc.contributor.author | Bishop, DT | |
dc.contributor.author | Reid, A | |
dc.contributor.author | Huddart, RA | |
dc.contributor.author | Shipley, J | |
dc.contributor.author | Grotmol, T | |
dc.contributor.author | Wiklund, F | |
dc.contributor.author | Houlston, RS | |
dc.contributor.author | Turnbull, C | |
dc.date.accessioned | 2017-07-20T09:46:25Z | |
dc.date.issued | 2017-07-01 | |
dc.identifier.citation | Nature genetics, 2017, 49 (7), pp. 1133 - 1140 | |
dc.identifier.issn | 1061-4036 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/732 | |
dc.identifier.eissn | 1546-1718 | |
dc.identifier.doi | 10.1038/ng.3896 | |
dc.description.abstract | Genome-wide association studies (GWAS) have transformed understanding of susceptibility to testicular germ cell tumors (TGCTs), but much of the heritability remains unexplained. Here we report a new GWAS, a meta-analysis with previous GWAS and a replication series, totaling 7,319 TGCT cases and 23,082 controls. We identify 19 new TGCT risk loci, roughly doubling the number of known TGCT risk loci to 44. By performing in situ Hi-C in TGCT cells, we provide evidence for a network of physical interactions among all 44 TGCT risk SNPs and candidate causal genes. Our findings implicate widespread disruption of developmental transcriptional regulators as a basis of TGCT susceptibility, consistent with failed primordial germ cell differentiation as an initiating step in oncogenesis. Defective microtubule assembly and dysregulation of KIT-MAPK signaling also feature as recurrently disrupted pathways. Our findings support a polygenic model of risk and provide insight into the biological basis of TGCT. | |
dc.format | Print-Electronic | |
dc.format.extent | 1133 - 1140 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | NATURE PUBLISHING GROUP | |
dc.rights.uri | https://www.rioxx.net/licenses/all-rights-reserved | |
dc.subject | UK Testicular Cancer Collaboration | |
dc.subject | PRACTICAL Consortium | |
dc.subject | Chromatin | |
dc.subject | Humans | |
dc.subject | Neoplasms, Germ Cell and Embryonal | |
dc.subject | Testicular Neoplasms | |
dc.subject | Genetic Predisposition to Disease | |
dc.subject | Risk | |
dc.subject | Gene Expression Profiling | |
dc.subject | Genotype | |
dc.subject | Polymorphism, Single Nucleotide | |
dc.subject | Adult | |
dc.subject | Middle Aged | |
dc.subject | Male | |
dc.subject | Genome-Wide Association Study | |
dc.subject | Young Adult | |
dc.subject | Molecular Sequence Annotation | |
dc.title | Identification of 19 new risk loci and potential regulatory mechanisms influencing susceptibility to testicular germ cell tumor. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2017-05-16 | |
rioxxterms.versionofrecord | 10.1038/ng.3896 | |
rioxxterms.licenseref.uri | https://www.rioxx.net/licenses/all-rights-reserved | |
rioxxterms.licenseref.startdate | 2017-07 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Nature genetics | |
pubs.issue | 7 | |
pubs.notes | Not known | |
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/Complex Trait Genetics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Sarcoma Molecular Pathology | |
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/Genetics and Epidemiology/Oncogenetics | |
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/Molecular Pathology/Sarcoma Molecular Pathology | |
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/Primary Group/ICR Divisions/Radiotherapy and Imaging/Oncogenetics | |
pubs.organisational-group | /ICR/Primary Group/Royal Marsden Clinical Units | |
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/Complex Trait Genetics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Sarcoma Molecular Pathology | |
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/Genetics and Epidemiology/Oncogenetics | |
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/Molecular Pathology/Sarcoma Molecular Pathology | |
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/Primary Group/ICR Divisions/Radiotherapy and Imaging/Oncogenetics | |
pubs.organisational-group | /ICR/Primary Group/Royal Marsden Clinical Units | |
pubs.publication-status | Published | |
pubs.volume | 49 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Complex Trait Genetics | |
icr.researchteam | Cancer Genomics | |
icr.researchteam | Molecular & Population Genetics | |
icr.researchteam | Sarcoma Molecular Pathology | |
icr.researchteam | Clinical Academic Radiotherapy (Huddart) | |
icr.researchteam | Oncogenetics | |
dc.contributor.icrauthor | Litchfield, Kevin | |
dc.contributor.icrauthor | Law, Philip | |
dc.contributor.icrauthor | Broderick, Peter | |
dc.contributor.icrauthor | Kote-Jarai, Zsofia | |
dc.contributor.icrauthor | Eeles, Rosalind | |
dc.contributor.icrauthor | Huddart, Robert | |
dc.contributor.icrauthor | Shipley, Janet | |
dc.contributor.icrauthor | Houlston, Richard | |
dc.contributor.icrauthor | Turnbull, Clare | |