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dc.contributor.authorLitchfield, K
dc.contributor.authorLevy, M
dc.contributor.authorHuddart, RA
dc.contributor.authorShipley, J
dc.contributor.authorTurnbull, C
dc.date.accessioned2016-11-23T13:07:36Z
dc.date.issued2016-07
dc.identifier.citationNature reviews. Urology, 2016, 13 (7), pp. 409 - 419
dc.identifier.issn1759-4812
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/247
dc.identifier.eissn1759-4820
dc.identifier.doi10.1038/nrurol.2016.107
dc.description.abstractThe genomic landscape of testicular germ cell tumour (TGCT) can be summarized using four overarching hypotheses. Firstly, TGCT risk is dominated by inherited genetic factors, which determine nearly half of all disease risk and are highly polygenic in nature. Secondly KIT-KITLG signalling is currently the major pathway that is implicated in TGCT formation, both as a predisposition risk factor and a somatic driver event. Results from genome-wide association studies have also consistently suggested that other closely related pathways involved in male germ cell development and sex determination are associated with TGCT risk. Thirdly, the method of disease formation is unique, with tumours universally stemming from a noninvasive precursor lesion, probably of fetal origin, which lies dormant through childhood into adolescence and then eventually begins malignant growth in early adulthood. Formation of a 12p isochromosome, a hallmark of TGCT observed in nearly all tumours, is likely to be a key triggering event for malignant transformation. Finally, TGCT have been shown to have a distinctive somatic mutational profile, with a low rate of point mutations contrasted with frequent large-scale chromosomal gains. These four hypotheses by no means constitute a complete model that explains TGCT tumorigenesis, but advances in genomic technologies have enabled considerable progress in describing and understanding the disease. Further advancing our understanding of the genomic basis of TGCT offers a clear opportunity for clinical benefit in terms of preventing invasive cancer arising in young men, decreasing the burden of chemotherapy-related survivorship issues and reducing mortality in the minority of patients who have treatment-refractory disease.
dc.formatPrint-Electronic
dc.format.extent409 - 419
dc.languageeng
dc.language.isoeng
dc.subjectHumans
dc.subjectNeoplasms, Germ Cell and Embryonal
dc.subjectTesticular Neoplasms
dc.subjectGenetic Predisposition to Disease
dc.subjectAntineoplastic Agents
dc.subjectTreatment Outcome
dc.subjectSurvival Rate
dc.subjectPolymorphism, Single Nucleotide
dc.subjectMale
dc.subjectGene Regulatory Networks
dc.titleThe genomic landscape of testicular germ cell tumours: from susceptibility to treatment.
dc.typeJournal Article
dcterms.dateAccepted2016-06-14
rioxxterms.versionofrecord10.1038/nrurol.2016.107
rioxxterms.licenseref.startdate2016-07
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfNature reviews. Urology
pubs.issue7
pubs.notes6 months
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/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Sarcoma Molecular Pathology
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
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
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/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.publication-statusPublished
pubs.volume13en_US
pubs.embargo.terms6 months
icr.researchteamMolecular & Population Geneticsen_US
icr.researchteamSarcoma Molecular Pathologyen_US
icr.researchteamClinical Academic Radiotherapy (Huddart)en_US
dc.contributor.icrauthorShipley, Janeten
dc.contributor.icrauthorTurnbull, Clareen
dc.contributor.icrauthorHuddart, Roberten
dc.contributor.icrauthorLitchfield, Kevinen


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