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SDH-deficient tumours are most commonly associated with a germline SDH subunit gene (<jats:italic>SDHA<\/jats:italic>\/<jats:italic>B<\/jats:italic>\/<jats:italic>C<\/jats:italic>\/<jats:italic>D<\/jats:italic>) mutation but can also be associated with epigenetic silencing of the <jats:italic>SDHC<\/jats:italic> gene. However, clinical diagnostic testing for an <jats:italic>SDHC<\/jats:italic> 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 <jats:italic>SDHC<\/jats:italic> epimutations in clinical practice. <jats:italic>SDHC<\/jats:italic> promoter methylation analysis of 32 paraffin embedded tumours (including 15 GIST and 17 PPGL) was performed using a pyrosequencing technique and correlated with <jats:italic>SDHC<\/jats:italic> gene expression. <jats:italic>SDHC<\/jats:italic> promoter methylation was identified in 6 (18.7%) tumours. All 6 <jats:italic>SDHC<\/jats:italic> epimutation cases presented with SDH deficient wtGIST and 3\/6 cases had multiple primary tumours. No case of constitutional <jats:italic>SDHC<\/jats:italic> promoter hypermethylation was detected. Whole genome sequencing of germline DNA from three wtGIST cases with an <jats:italic>SDHC<\/jats:italic> epimutation, did not reveal any causative sequence anomalies. Herein, we recommend a diagnostic workflow for the detection of an <jats:italic>SDHC<\/jats:italic> epimutation in a service setting.<\/jats:p>","DOI":"10.1038\/s41598-019-46124-9","type":"journal-article","created":{"date-parts":[[2019,7,15]],"date-time":"2019-07-15T10:50:58Z","timestamp":1563187858000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["SDHC epi-mutation testing in gastrointestinal stromal tumours and related tumours in clinical practice"],"prefix":"10.1038","volume":"9","author":[{"given":"Ruth T.","family":"Casey","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rogier","family":"ten Hoopen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eguzkine","family":"Ochoa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin G.","family":"Challis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Whitworth","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip S.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jose Ezequiel","family":"Martin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Graeme R.","family":"Clark","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fay","family":"Rodger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mel","family":"Maranian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kieren","family":"Allinson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5844-856X","authenticated-orcid":false,"given":"Basetti","family":"Madhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Roberts","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4317-0013","authenticated-orcid":false,"given":"Luis","family":"Campos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joanne","family":"Anstee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soo-Mi","family":"Park","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alison","family":"Marker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colin","family":"Watts","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Venkata R.","family":"Bulusu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olivier T.","family":"Giger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6226-6918","authenticated-orcid":false,"given":"Eamonn R.","family":"Maher","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,7,15]]},"reference":[{"key":"46124_CR1","doi-asserted-by":"publisher","first-page":"e8","DOI":"10.1371\/journal.pgen.0010008","volume":"1","author":"PLM Dahia","year":"2005","unstructured":"Dahia, P. 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