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dc.contributor.authorCastle, Bruce
dc.contributor.authorSansbury, Francis H
dc.date.accessioned2021-02-23T10:02:05Z
dc.date.available2021-02-23T10:02:05Z
dc.date.issued2021-01
dc.identifier.citationSmith PS et al. Pathogenic germline variants in patients with features of hereditary renal cell carcinoma: Evidence for further locus heterogeneity. Genes Chromosomes Cancer. 2021 Jan;60(1):5-16. doi: 10.1002/gcc.22893. Epub 2020 Sep 19.en_US
dc.identifier.pmid32830346
dc.identifier.doi10.1002/gcc.22893
dc.identifier.urihttps://rde.dspace-express.com/handle/11287/621628
dc.description.abstractInherited renal cell carcinoma (RCC) is associated with multiple familial cancer syndromes but most individuals with features of non-syndromic inherited RCC do not harbor variants in the most commonly tested renal cancer predisposition genes (CPGs). We investigated whether undiagnosed cases might harbor mutations in CPGs that are not routinely tested for by testing 118 individuals with features suggestive of inherited RCC (family history of RCC, two or more primary RCC aged <60 years, or early onset RCC ≤46 years) for the presence of pathogenic variants in a large panel of CPGs. All individuals had been prescreened for pathogenic variants in the major RCC genes. We detected pathogenic or likely pathogenic (P/LP) variants of potential clinical relevance in 16.1% (19/118) of individuals, including P/LP variants in BRIP1 (n = 4), CHEK2 (n = 3), MITF (n = 1), and BRCA1 (n = 1). Though the power to detect rare variants was limited by sample size the frequency of truncating variants in BRIP1, 4/118, was significantly higher than in controls (P = 5.92E-03). These findings suggest that the application of genetic testing for larger inherited cancer gene panels in patients with indicators of a potential inherited RCC can increase the diagnostic yield for P/LP variants. However, the clinical utility of such a diagnostic strategy requires validation and further evaluation and in particular, confirmation of rarer RCC genotype-phenotype associations is required.en_US
dc.language.isoenen_US
dc.publisherWileyen_US
dc.relation.urlhttps://doi.org/10.1002/gcc.22893en_US
dc.rights© 2020 The Authors. Genes, Chromosomes and Cancer published by Wiley Periodicals LLC. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.en_US
dc.rightsCC0 1.0 Universal*
dc.rights.urihttp://creativecommons.org/publicdomain/zero/1.0/*
dc.subjectinheriteden_US
dc.subjectpredispositionen_US
dc.subjectrenal cell carcinomaen_US
dc.titlePathogenic germline variants in patients with features of hereditary renal cell carcinoma: Evidence for further locus heterogeneityen_US
dc.typeJournal Articleen_US
dc.identifier.journalGenes, Chromosomes and Canceren_US
dc.description.noteThis article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.en_US
dc.description.fundingCancer Research UK H2020 European Research Council. Grant Number: OncoTreat National Institute for Health Researchen_US
dc.type.versionPublisheden_US
dc.description.admin-notepublished version, accepted version (12 month embargo), submitted versionen_US


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© 2020 The Authors. Genes, Chromosomes and Cancer published by Wiley Periodicals LLC.

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Except where otherwise noted, this item's license is described as © 2020 The Authors. Genes, Chromosomes and Cancer published by Wiley Periodicals LLC. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.