Show simple item record

dc.contributor.authorCasey, Ruthen
dc.contributor.authorTen Hoopen, Rogieren
dc.contributor.authorOchoa, Eguzkineen
dc.contributor.authorChallis, Benjamin Gen
dc.contributor.authorWhitworth, Jamesen
dc.contributor.authorSmith, Philipen
dc.contributor.authorMartin, Jose Ezequielen
dc.contributor.authorClark, Graeme Ren
dc.contributor.authorRodger, Fayen
dc.contributor.authorMaranian, Melen
dc.contributor.authorAllinson, Kierenen
dc.contributor.authorMadhu, Basettien
dc.contributor.authorRoberts, Thomasen
dc.contributor.authorCampos, Luisen
dc.contributor.authorAnstee, Joanneen
dc.contributor.authorPark, Soo-Mien
dc.contributor.authorMarker, Alisonen
dc.contributor.authorWatts, Colinen
dc.contributor.authorBulusu, Venkata Ren
dc.contributor.authorGiger, Olivieren
dc.contributor.authorMaher, Eamonnen
dc.date.accessioned2019-06-17T23:31:51Z
dc.date.available2019-06-17T23:31:51Z
dc.date.issued2019-07-15en
dc.identifier.issn2045-2322
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/293704
dc.description.abstractThe enzyme succinate dehydrogenase (SDH) functions in the citric acid cycle and loss of function predisposes to the development of phaeochromocytoma/paraganglioma (PPGL), wild type gastrointestinal stromal tumour (wtGIST) and renal cell carcinoma. SDH-deficient tumours are most commonly associated with a germline SDH subunit gene (SDHA/B/C/D) mutation but can also be associated with epigenetic silencing of the SDHC gene. However, clinical diagnostic testing for an SDHC epimutation is not widely available. The objective of this study was to investigate the indications for and the optimum diagnostic pathways for the detection of SDHC epimutations in clinical practice. SDHC promoter methylation analysis of 32 paraffin embedded tumours (including 15 GIST and 17 PPGL) was performed using a pyrosequencing technique and correlated with SDHC gene expression. SDHC promoter methylation was identified in 6 (18.7%) tumours. All 6 SDHC epimutation cases presented with SDH deficient wtGIST and 3/6 cases had multiple primary tumours. No case of constitutional SDHC promoter hypermethylation was detected. Whole genome sequencing of germline DNA from three wtGIST cases with an SDHC epimutation, did not reveal any causative sequence anomalies. Herein, we recommend a diagnostic workflow for the detection of an SDHC epimutation in a service setting.
dc.description.sponsorshipHealth Research Board Ireland and GIST Support UK (RTC), NIHR Senior Investigator Award (ERM), European Research Council Advanced Researcher Award (ERM), the British Heart Foundation (ERM). The University of Cambridge has received salary support in respect of ERM from the NHS in the East of England through the Clinical
dc.format.mediumElectronicen
dc.languageengen
dc.publisherNature Publishing Group
dc.rightsAll rights reserved
dc.rights.uri
dc.subjectHumansen
dc.subjectParagangliomaen
dc.subjectPheochromocytomaen
dc.subjectAdrenal Gland Neoplasmsen
dc.subjectGastrointestinal Stromal Tumorsen
dc.subjectSuccinate Dehydrogenaseen
dc.subjectMembrane Proteinsen
dc.subjectDNA Methylationen
dc.subjectEpigenesis, Geneticen
dc.subjectMutationen
dc.subjectGerm-Line Mutationen
dc.subjectGenes, Regulatoren
dc.subjectAdolescenten
dc.subjectAdulten
dc.subjectAgeden
dc.subjectMiddle Ageden
dc.subjectFemaleen
dc.subjectMaleen
dc.subjectPromoter Regions, Geneticen
dc.subjectEpigenomicsen
dc.subjectHigh-Throughput Nucleotide Sequencingen
dc.subjectTranscriptomeen
dc.titleSDHC epi-mutation testing in gastrointestinal stromal tumours and related tumours in clinical practice.en
dc.typeArticle
prism.issueIdentifier1en
prism.publicationDate2019en
prism.publicationNameScientific reportsen
prism.startingPage10244
prism.volume9en
dc.identifier.doi10.17863/CAM.40816
dcterms.dateAccepted2019-06-07en
rioxxterms.versionofrecord10.1038/s41598-019-46124-9en
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2019-07-15en
dc.contributor.orcidTen Hoopen, Rogier [0000-0003-0655-9182]
dc.contributor.orcidOchoa, Eguzkine [0000-0002-1506-9065]
dc.contributor.orcidWhitworth, James [0000-0002-3682-2298]
dc.contributor.orcidSmith, Philip [0000-0002-9306-1747]
dc.contributor.orcidMadhu, Basetti [0000-0001-5844-856X]
dc.contributor.orcidCampos, Luis [0000-0002-4317-0013]
dc.contributor.orcidGiger, Olivier [0000-0003-3390-6397]
dc.contributor.orcidMaher, Eamonn [0000-0002-6226-6918]
dc.identifier.eissn2045-2322
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idCambridge University Hospitals NHS Foundation Trust (CUH) (BRC 2012-2017)
pubs.funder-project-idCambridge University Hospitals NHS Foundation Trust (CUH) (BRC 2012-2017)
pubs.funder-project-idCancer Research UK (C20/A20917)
cam.orpheus.successMon Jun 08 08:21:10 BST 2020 - The item has an open VoR version.*
rioxxterms.freetoread.startdate2022-06-17


Files in this item

Thumbnail
Thumbnail

This item appears in the following Collection(s)

Show simple item record