Investigating the role of somatic sequencing platforms for phaeochromocytoma and paraganglioma in a large UK cohort.
dc.contributor.author | Winzeler, Bettina | |
dc.contributor.author | Tufton, Nicola | |
dc.contributor.author | S Lim, Eugenie | |
dc.contributor.author | Challis, Ben G | |
dc.contributor.author | Park, Soo-Mi | |
dc.contributor.author | Izatt, Louise | |
dc.contributor.author | Carroll, Paul V | |
dc.contributor.author | Velusamy, Anand | |
dc.contributor.author | Hulse, Tony | |
dc.contributor.author | Whitelaw, Benjamin C | |
dc.contributor.author | Martin, Ezequiel | |
dc.contributor.author | Rodger, Fay | |
dc.contributor.author | Maranian, Melanie | |
dc.contributor.author | Clark, Graeme R | |
dc.contributor.author | A Akker, Scott | |
dc.contributor.author | Maher, Eamonn | |
dc.contributor.author | Casey, Ruth T | |
dc.date.accessioned | 2021-12-18T00:30:31Z | |
dc.date.available | 2021-12-18T00:30:31Z | |
dc.date.issued | 2021-12-06 | |
dc.identifier.issn | 0300-0664 | |
dc.identifier.uri | https://www.repository.cam.ac.uk/handle/1810/331602 | |
dc.description.abstract | OBJECTIVES: Phaeochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumours with malignant potential and a hereditary basis in almost 40% of patients. Germline genetic testing has transformed the management of PPGL enabling stratification of surveillance approaches, earlier diagnosis and predictive testing of at-risk family members. Recent studies have identified somatic mutations in a further subset of patients, indicating that molecular drivers at either a germline or tumour level can be identified in up to 80% of PPGL cases. The aim of this study was to investigate the clinical utility of somatic sequencing in a large cohort of patients with PPGL in the United Kingdom. DESIGN AND PATIENTS: Prospectively collected matched germline and tumour samples (development cohort) and retrospectively collected tumour samples (validation cohort) of patients with PPGL were investigated. MEASUREMENTS: Clinical characteristics of patients were assessed and tumour and germline DNA was analysed using a next-generation sequencing strategy. A screen for variants within 'mutation hotspots' in 68 human cancer genes was performed. RESULTS: Of 141 included patients, 45 (32%) had a germline mutation. In 37 (26%) patients one or more driver somatic variants were identified including 26 likely pathogenic or pathogenic variants and 19 variants of uncertain significance. Pathogenic somatic variants, observed in 25 (18%) patients, were most commonly identified in the VHL, NF1, HRAS and RET genes. Pathogenic somatic variants were almost exclusively identified in patients without a germline mutation (all but one), suggesting that somatic sequencing is likely to be most informative for those patients with negative germline genetic test results. CONCLUSIONS: Somatic sequencing may further stratify surveillance approaches for patients without a germline genetic driver and may also inform targeted therapeutic strategies for patients with metastatic disease. | |
dc.publisher | Wiley | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 International | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.subject | paraganglioma | |
dc.subject | phaeochromocytoma | |
dc.subject | somatic variant | |
dc.title | Investigating the role of somatic sequencing platforms for phaeochromocytoma and paraganglioma in a large UK cohort. | |
dc.type | Article | |
dc.publisher.department | Department of Medical Genetics | |
dc.date.updated | 2021-12-16T15:13:32Z | |
prism.publicationDate | 2021 | |
prism.publicationName | Clin Endocrinol (Oxf) | |
dc.identifier.doi | 10.17863/CAM.79054 | |
dcterms.dateAccepted | 2021-10-21 | |
rioxxterms.versionofrecord | 10.1111/cen.14639 | |
rioxxterms.version | VoR | |
dc.contributor.orcid | Winzeler, Bettina [0000-0001-8305-2700] | |
dc.contributor.orcid | Tufton, Nicola [0000-0003-2382-9711] | |
dc.contributor.orcid | Challis, Ben G [0000-0002-1130-2851] | |
dc.contributor.orcid | Izatt, Louise [0000-0003-1258-4843] | |
dc.contributor.orcid | A Akker, Scott [0000-0003-3893-3116] | |
dc.contributor.orcid | Maher, Eamonn [0000-0002-6226-6918] | |
dc.contributor.orcid | Casey, Ruth T [0000-0003-4058-3135] | |
dc.identifier.eissn | 1365-2265 | |
rioxxterms.type | Journal Article/Review | |
cam.issuedOnline | 2021-12-06 | |
cam.depositDate | 2021-12-16 | |
pubs.licence-identifier | apollo-deposit-licence-2-1 | |
pubs.licence-display-name | Apollo Repository Deposit Licence Agreement |
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