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dc.contributor.authorCasey, Ruth T.
dc.contributor.authorten Hoopen, Rogier
dc.contributor.authorOchoa, Eguzkine
dc.contributor.authorChallis, Benjamin G.
dc.contributor.authorWhitworth, James
dc.contributor.authorSmith, Philip S.
dc.contributor.authorMartin, Jose Ezequiel
dc.contributor.authorClark, Graeme R.
dc.contributor.authorRodger, Fay
dc.contributor.authorMaranian, Mel
dc.contributor.authorAllinson, Kieren
dc.contributor.authorMadhu, Basetti
dc.contributor.authorRoberts, Thomas
dc.contributor.authorCampos, Luis
dc.contributor.authorAnstee, Joanne
dc.contributor.authorPark, Soo-Mi
dc.contributor.authorMarker, Alison
dc.contributor.authorWatts, Colin
dc.contributor.authorBulusu, Venkata R.
dc.contributor.authorGiger, Olivier T.
dc.contributor.authorMaher, Eamonn R.
dc.date.accessioned2020-07-14T15:12:28Z
dc.date.available2020-07-14T15:12:28Z
dc.date.issued2019-07-15
dc.date.submitted2019-03-18
dc.identifier.others41598-019-46124-9
dc.identifier.other46124
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/307935
dc.description.abstractAbstract: The 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.languageen
dc.publisherNature Publishing Group UK
dc.rightsAttribution 4.0 International (CC BY 4.0)en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectArticle
dc.subject/692/4017
dc.subject/692/4028
dc.subject/45/22
dc.subject/45/23
dc.subject/45/90
dc.subject/45/91
dc.subjectarticle
dc.titleSDHC epi-mutation testing in gastrointestinal stromal tumours and related tumours in clinical practice
dc.typeArticle
dc.date.updated2020-07-14T15:12:28Z
prism.issueIdentifier1
prism.publicationNameScientific Reports
prism.volume9
dc.identifier.doi10.17863/CAM.55027
dcterms.dateAccepted2019-06-07
rioxxterms.versionofrecord10.1038/s41598-019-46124-9
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidMadhu, Basetti [0000-0001-5844-856X]
dc.contributor.orcidCampos, Luis [0000-0002-4317-0013]
dc.contributor.orcidMaher, Eamonn R. [0000-0002-6226-6918]
dc.identifier.eissn2045-2322


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Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's licence is described as Attribution 4.0 International (CC BY 4.0)