SDHC epi-mutation testing in gastrointestinal stromal tumours and related tumours in clinical practice
| Autor: | Venkata R. Bulusu, Philip Smith, James Whitworth, Basetti Madhu, Graeme R. Clark, Thomas Roberts, Alison Marker, Kieren Allinson, Ruth T Casey, Soo-Mi Park, Mel Maranian, Olivier Giger, Eguzkine Ochoa, Jose Ezequiel Martin, Colin Watts, Rogier ten Hoopen, Joanne Anstee, Fay Rodger, Eamonn R. Maher, Luis Miguel Pino Campos, Benjamin G. Challis |
|---|---|
| Přispěvatelé: | Madhu, Basetti [0000-0001-5844-856X], Campos, Luis [0000-0002-4317-0013], Maher, Eamonn R [0000-0002-6226-6918], Apollo - University of Cambridge Repository, Maher, Eamonn R. [0000-0002-6226-6918] |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Epigenomics Male SDHA Adrenal Gland Neoplasms medicine.disease_cause Germline Epigenesis Genetic 0302 clinical medicine Renal cell carcinoma Paraganglioma Genes Regulator Promoter Regions Genetic 45/90 Mutation Multidisciplinary Molecular medicine GiST article High-Throughput Nucleotide Sequencing Middle Aged Succinate Dehydrogenase Oncology Medicine Female Adult Adolescent Gastrointestinal Stromal Tumors Science 45/22 45/23 Pheochromocytoma 692/4028 03 medical and health sciences medicine Humans Loss function Germ-Line Mutation Aged 45/91 business.industry Membrane Proteins DNA Methylation medicine.disease 692/4017 030104 developmental biology Mutation testing Cancer research business Transcriptome 030217 neurology & neurosurgery |
| Zdroj: | Scientific Reports, Vol 9, Iss 1, Pp 1-10 (2019) Scientific Reports |
| DOI: | 10.17863/cam.55027 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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