{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T15:27:35Z","timestamp":1791559655480,"version":"4.3.4"},"reference-count":56,"publisher":"Oxford University Press (OUP)","issue":"16","license":[{"start":{"date-parts":[[2022,3,21]],"date-time":"2022-03-21T00:00:00Z","timestamp":1647820800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C1298\/A8362"],"award-info":[{"award-number":["C1298\/A8362"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,8,23]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Around 95% of patients with clinical features that meet the diagnostic criteria for von Hippel\u2013Lindau disease (VHL) have a detectable inactivating germline variant in VHL. The VHL protein (pVHL) functions as part of the E3 ubiquitin ligase complex comprising pVHL, elongin C, elongin B, cullin 2 and ring box 1 (VCB-CR complex), which plays a key role in oxygen sensing and degradation of hypoxia-inducible factors. To date, only variants in VHL have been shown to cause VHL disease. We undertook trio analysis by whole-exome sequencing in a proband with VHL disease but without a detectable VHL mutation. Molecular studies were also performed on paired DNA extracted from the proband\u2019s kidney tumour and blood and bioinformatics analysis of sporadic renal cell carcinoma (RCC) dataset was undertaken. A de novo pathogenic variant in ELOC NM_005648.4(ELOC):c.236A&amp;gt;G (p.Tyr79Cys) gene was identified in the proband. ELOC encodes elongin C, a key component [C] of the VCB-CR complex. The p.Tyr79Cys substitution is a mutational hotspot in sporadic VHL-competent RCC and has previously been shown to mimic the effects of pVHL deficiency on hypoxic signalling. Analysis of an RCC from the proband showed similar findings to that in somatically ELOC-mutated RCC (expression of hypoxia-responsive proteins, no somatic VHL variants and chromosome 8 loss). These findings are consistent with pathogenic ELOC variants being a novel cause for VHL disease and suggest that genetic testing for ELOC variants should be performed in individuals with suspected VHL disease with no detectable VHL variant.<\/jats:p>","DOI":"10.1093\/hmg\/ddac066","type":"journal-article","created":{"date-parts":[[2022,3,18]],"date-time":"2022-03-18T20:16:00Z","timestamp":1647634560000},"page":"2728-2737","source":"Crossref","is-referenced-by-count":36,"title":["Elongin C (<i>ELOC<\/i>\/<i>TCEB1<\/i>)-associated von Hippel\u2013Lindau disease"],"prefix":"10.1093","volume":"31","author":[{"given":"Avgi","family":"Andreou","sequence":"first","affiliation":[{"name":"Department of Medical Genetics , University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryndis","family":"Yngvadottir","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics , University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laia","family":"Bassaganyas","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics , University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graeme","family":"Clark","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics , University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK"},{"name":"Stratified Medicine Core Laboratory NGS Hub , Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ezequiel","family":"Martin","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics , University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK"},{"name":"Stratified Medicine Core Laboratory NGS Hub , Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Whitworth","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics , University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex J","family":"Cornish","sequence":"additional","affiliation":[{"name":"Division of Genetics and Epidemiology , The Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Genomics England Research Consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard S","family":"Houlston","sequence":"additional","affiliation":[{"name":"Division of Genetics and Epidemiology , The Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Rich","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology , St. George\u2019s University Hospitals NHS Foundation Trust, London SW17 0QT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Egan","sequence":"additional","affiliation":[{"name":"NIHR Biomedical Research Center at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology , London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shirley V","family":"Hodgson","sequence":"additional","affiliation":[{"name":"South West Thames Regional Genetics Service , St George's University Hospitals NHS Foundation Trust, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne Y","family":"Warren","sequence":"additional","affiliation":[{"name":"Department of Histopathology , Cambridge University NHS Foundation Trust, Cambridge CB2 OQQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie","family":"Snape","sequence":"additional","affiliation":[{"name":"South West Thames Regional Genetics Service , St George's University Hospitals NHS Foundation Trust, London, UK"},{"name":"St George's University of London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6226-6918","authenticated-orcid":false,"given":"Eamonn R","family":"Maher","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics , University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,3,21]]},"reference":[{"key":"2022082420172684000_ref1","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/nrc3844","article-title":"VHL, the story of a tumour suppressor gene","volume":"15","author":"Gossage","year":"2015","journal-title":"Nat. Rev. Cancer"},{"key":"2022082420172684000_ref2","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1093\/qjmed\/77.2.1151","article-title":"Clinical features and natural history of von Hippel-Lindau disease","volume":"77","author":"Maher","year":"1990","journal-title":"Q. J. Med."},{"key":"2022082420172684000_ref3","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/0002-9343(64)90107-X","article-title":"Lindau\u2019s disease. Review of the literature and study of a large kindred","volume":"36","author":"Melmon","year":"1964","journal-title":"Am. J. Med."},{"key":"2022082420172684000_ref4","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1136\/jmg.28.7.443","article-title":"Von Hippel-Lindau disease: a genetic study","volume":"28","author":"Maher","year":"1991","journal-title":"J. Med. 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A."},{"key":"2022082420172684000_ref17","first-page":"3014","article-title":"VHL-mediated hypoxia regulation of cyclin D1 in renal carcinoma cells","volume":"62","author":"Bindra","year":"2002","journal-title":"Cancer Res."},{"key":"2022082420172684000_ref18","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1126\/science.284.5413.455","article-title":"Structure of the VHL-ElonginC-ElonginB complex: implications for VHL tumor suppressor function","volume":"284","author":"Stebbins","year":"1999","journal-title":"Science"},{"key":"2022082420172684000_ref19","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1126\/science.1059817","article-title":"HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing","volume":"292","author":"Ivan","year":"2001","journal-title":"Science"},{"key":"2022082420172684000_ref20","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1038\/modpathol.2015.6","article-title":"TCEB1-mutated renal cell carcinoma: a distinct genomic and morphological subtype","volume":"28","author":"Hakimi","year":"2015","journal-title":"Mod. 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Genet."},{"key":"2022082420172684000_ref25","volume-title":"The PyMOL Molecular Graphics System","author":"Schrodinger","year":"2010"},{"key":"2022082420172684000_ref26","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.str.2014.12.014","article-title":"Insights into Cullin-RING E3 ubiquitin ligase recruitment: structure of the VHL-EloBC-Cul2 complex","volume":"23","author":"Nguyen","year":"2015","journal-title":"Structure"},{"key":"2022082420172684000_ref27","doi-asserted-by":"crossref","first-page":"4674","DOI":"10.1158\/0008-5472.CAN-09-0146","article-title":"Patterns of gene expression and copy-number alterations in von-Hippel Lindau disease-associated and sporadic clear cell carcinoma of the kidney","volume":"69","author":"Beroukhim","year":"2009","journal-title":"Cancer Res."},{"key":"2022082420172684000_ref28","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.celrep.2018.03.075","article-title":"The Cancer Genome Atlas comprehensive molecular characterization of renal cell carcinoma","volume":"23","author":"Ricketts","year":"2018","journal-title":"Cell Rep."},{"key":"2022082420172684000_ref29","volume-title":"The national genomics research and healthcare knowledgebase","author":"Caulfield","year":"2017"},{"key":"2022082420172684000_ref30","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.1093\/hmg\/11.13.1549","article-title":"The \u2018just-right\u2019 signaling model: APC somatic mutations are selected based on a specific level of activation of the beta-catenin signaling cascade","volume":"11","author":"Albuquerque","year":"2002","journal-title":"Hum. Mol. Genet."},{"key":"2022082420172684000_ref31","doi-asserted-by":"crossref","first-page":"31972","DOI":"10.1074\/jbc.M303170200","article-title":"Tyrosine phosphorylation disrupts elongin interaction and accelerates SOCS3 degradation","volume":"278","author":"Haan","year":"2003","journal-title":"J. Biol. Chem."},{"key":"2022082420172684000_ref32","doi-asserted-by":"crossref","first-page":"14005","DOI":"10.1074\/jbc.C000106200","article-title":"Suppressor of cytokine signaling-1 inhibits VAV function through protein degradation","volume":"275","author":"De Sepulveda","year":"2000","journal-title":"J. Biol. Chem."},{"key":"2022082420172684000_ref33","doi-asserted-by":"crossref","first-page":"12530","DOI":"10.1074\/jbc.M010074200","article-title":"The SOCS box of SOCS-1 accelerates ubiquitin-dependent proteolysis of TEL-JAK2","volume":"276","author":"Kamizono","year":"2001","journal-title":"J. Biol. Chem."},{"key":"2022082420172684000_ref34","doi-asserted-by":"crossref","first-page":"42394","DOI":"10.1074\/jbc.C200444200","article-title":"SOCS-1 and SOCS-3 block insulin signaling by ubiquitin-mediated degradation of IRS1 and IRS2","volume":"277","author":"Rui","year":"2002","journal-title":"J. Biol. Chem."},{"key":"2022082420172684000_ref35","doi-asserted-by":"crossref","first-page":"7637","DOI":"10.1073\/pnas.0601638103","article-title":"Crystal structure of the SOCS2-elongin C-elongin B complex defines a prototypical SOCS box ubiquitin ligase","volume":"103","author":"Bullock","year":"2006","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2022082420172684000_ref36","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1038\/ncb1201-1114","article-title":"Design and application of a cytokine-receptor-based interaction trap","volume":"3","author":"Eyckerman","year":"2001","journal-title":"Nat. Cell Biol."},{"key":"2022082420172684000_ref37","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1038\/nature12222","article-title":"Comprehensive molecular characterization of clear cell renal cell carcinoma","volume":"499","author":"Cancer Genome Atlas Research Network","year":"2013","journal-title":"Nature"},{"key":"2022082420172684000_ref38","doi-asserted-by":"crossref","first-page":"5777","DOI":"10.1002\/cncr.27607","article-title":"Gain of chromosome 8q is associated with metastases and poor survival of patients with clear cell renal cell carcinoma","volume":"118","author":"Klatte","year":"2012","journal-title":"Cancer"},{"key":"2022082420172684000_ref39","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1177\/1756287217732660","article-title":"The correlation between gain of chromosome 8q and survival in patients with clear and papillary renal cell carcinoma","volume":"10","author":"Mehrazin","year":"2018","journal-title":"Ther. Adv. Urol."},{"key":"2022082420172684000_ref40","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1038\/ejhg.2010.175","article-title":"von Hippel-Lindau disease: a clinical and scientific review","volume":"19","author":"Maher","year":"2011","journal-title":"Eur. J. Hum. Genet."},{"key":"2022082420172684000_ref41","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1038\/nature19796","article-title":"Targeting renal cell carcinoma with a HIF-2 antagonist","volume":"539","author":"Chen","year":"2016","journal-title":"Nature"},{"key":"2022082420172684000_ref42","volume-title":"Illumina DNA Prep with Enrichment","author":"Illumina"},{"key":"2022082420172684000_ref43","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","article-title":"Fast and accurate short read alignment with Burrows-Wheeler transform","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"2022082420172684000_ref44","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","article-title":"The Sequence Alignment\/Map format and SAMtools","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"2022082420172684000_ref45","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1101\/gr.107524.110","article-title":"The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data","volume":"20","author":"McKenna","year":"2010","journal-title":"Genome Res."},{"key":"2022082420172684000_ref46","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1038\/ng.806","article-title":"A framework for variation discovery and genotyping using next-generation DNA sequencing data","volume":"43","author":"DePristo","year":"2011","journal-title":"Nat. Genet."},{"key":"2022082420172684000_ref47","doi-asserted-by":"crossref","first-page":"11.10.11","DOI":"10.1002\/0471250953.bi1110s43","article-title":"From FastQ data to high confidence variant calls: the Genome Analysis Toolkit best practices pipeline","volume":"43","author":"Van der Auwera","year":"2013","journal-title":"Curr. Protoc. Bioinform."},{"key":"2022082420172684000_ref48","doi-asserted-by":"crossref","first-page":"2156","DOI":"10.1093\/bioinformatics\/btr330","article-title":"The variant call format and VCFtools","volume":"27","author":"Danecek","year":"2011","journal-title":"Bioinformatics"},{"key":"2022082420172684000_ref49","doi-asserted-by":"crossref","first-page":"e164","DOI":"10.1093\/nar\/gkq603","article-title":"ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data","volume":"38","author":"Wang","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"2022082420172684000_ref50","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1186\/s13059-016-0974-4","article-title":"The Ensembl variant effect predictor","volume":"17","author":"McLaren","year":"2016","journal-title":"Genome Biol."},{"key":"2022082420172684000_ref51","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1093\/bioinformatics\/btq033","article-title":"BEDTools: a flexible suite of utilities for comparing genomic features","volume":"26","author":"Quinlan","year":"2010","journal-title":"Bioinformatics"},{"key":"2022082420172684000_ref52","doi-asserted-by":"crossref","first-page":"i333","DOI":"10.1093\/bioinformatics\/bts378","article-title":"DELLY: structural variant discovery by integrated paired-end and split-read analysis","volume":"28","author":"Rausch","year":"2012","journal-title":"Bioinformatics"},{"key":"2022082420172684000_ref53","volume-title":"Somatic copy number variant discovery (CNVs)","author":"GATK team"},{"key":"2022082420172684000_ref54","volume-title":"Illumina Microarray Solutions","author":"Illumina"},{"key":"2022082420172684000_ref55","volume-title":"Sanger Sequencing at Eurofins Genomics","author":"Eurofins"},{"key":"2022082420172684000_ref56","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1016\/j.cell.2012.04.023","article-title":"The life history of 21 breast cancers","volume":"149","author":"Nik-Zainal","year":"2012","journal-title":"Cell"}],"container-title":["Human Molecular Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/hmg\/advance-article-pdf\/doi\/10.1093\/hmg\/ddac066\/43409137\/ddac066.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/hmg\/article-pdf\/31\/16\/2728\/45499311\/ddac066.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/hmg\/article-pdf\/31\/16\/2728\/45499311\/ddac066.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,29]],"date-time":"2023-01-29T13:54:01Z","timestamp":1675000441000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/hmg\/article\/31\/16\/2728\/6551617"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,21]]},"references-count":56,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2022,3,21]]},"published-print":{"date-parts":[[2022,8,23]]}},"URL":"https:\/\/doi.org\/10.1093\/hmg\/ddac066","relation":{},"ISSN":["0964-6906","1460-2083"],"issn-type":[{"value":"0964-6906","type":"print"},{"value":"1460-2083","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,8,15]]},"published":{"date-parts":[[2022,3,21]]}}}