dc.contributor.author | Yost, S | |
dc.contributor.author | de Wolf, B | |
dc.contributor.author | Hanks, S | |
dc.contributor.author | Zachariou, A | |
dc.contributor.author | Marcozzi, C | |
dc.contributor.author | Clarke, M | |
dc.contributor.author | de Voer, R | |
dc.contributor.author | Etemad, B | |
dc.contributor.author | Uijttewaal, E | |
dc.contributor.author | Ramsay, E | |
dc.contributor.author | Wylie, H | |
dc.contributor.author | Elliott, A | |
dc.contributor.author | Picton, S | |
dc.contributor.author | Smith, A | |
dc.contributor.author | Smithson, S | |
dc.contributor.author | Seal, S | |
dc.contributor.author | Ruark, E | |
dc.contributor.author | Houge, G | |
dc.contributor.author | Pines, J | |
dc.contributor.author | Kops, GJPL | |
dc.contributor.author | Rahman, N | |
dc.date.accessioned | 2017-11-01T10:58:14Z | |
dc.date.issued | 2017-07-01 | |
dc.identifier.citation | Nature genetics, 2017, 49 (7), pp. 1148 - 1151 | |
dc.identifier.issn | 1061-4036 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/884 | |
dc.identifier.eissn | 1546-1718 | |
dc.identifier.doi | 10.1038/ng.3883 | |
dc.description.abstract | Through 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. | |
dc.format | Print-Electronic | |
dc.format.extent | 1148 - 1151 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | NATURE PORTFOLIO | |
dc.rights.uri | https://www.rioxx.net/licenses/under-embargo-all-rights-reserved | |
dc.subject | Humans | |
dc.subject | Sertoli-Leydig Cell Tumor | |
dc.subject | Ovarian Neoplasms | |
dc.subject | Kidney Neoplasms | |
dc.subject | Neoplasms, Multiple Primary | |
dc.subject | Microcephaly | |
dc.subject | Seizures | |
dc.subject | Aneuploidy | |
dc.subject | Genetic Predisposition to Disease | |
dc.subject | Protein-Serine-Threonine Kinases | |
dc.subject | Carrier Proteins | |
dc.subject | Cell Cycle Proteins | |
dc.subject | Microtubule-Associated Proteins | |
dc.subject | Nuclear Proteins | |
dc.subject | DNA, Neoplasm | |
dc.subject | Developmental Disabilities | |
dc.subject | Chromosome Segregation | |
dc.subject | RNA Stability | |
dc.subject | Mutation | |
dc.subject | Mosaicism | |
dc.subject | Child, Preschool | |
dc.subject | Female | |
dc.subject | Wilms Tumor | |
dc.subject | Leukemia, Myeloid, Acute | |
dc.subject | M Phase Cell Cycle Checkpoints | |
dc.subject | ATPases Associated with Diverse Cellular Activities | |
dc.title | Biallelic TRIP13 mutations predispose to Wilms tumor and chromosome missegregation. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2017-05-01 | |
rioxxterms.funder | The Institute of Cancer Research | |
rioxxterms.identifier.project | Unspecified | |
rioxxterms.versionofrecord | 10.1038/ng.3883 | |
rioxxterms.licenseref.uri | https://www.rioxx.net/licenses/under-embargo-all-rights-reserved | |
rioxxterms.licenseref.startdate | 2017-07 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Nature genetics | |
pubs.issue | 7 | |
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/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.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-status | Published | |
pubs.volume | 49 | |
pubs.embargo.terms | No embargo | |
icr.researchteam | Genetic Susceptibility | |
dc.contributor.icrauthor | Clarke, Matthew | |
dc.contributor.icrauthor | Pines, Jonathon | |