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dc.contributor.authorStewart, Granten
dc.date.accessioned2020-10-09T11:27:16Z
dc.date.available2020-10-09T11:27:16Z
dc.identifier.issn2473-4284
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/311287
dc.description.abstractIntroduction: A challenge in the diagnosis of renal cell carcinoma (RCC) is to distinguish chromophobe renal cell carcinoma (chRCC) from benign renal oncocytoma, as these tumor types are histologically and morphologically similar, yet they require different clinical management. Molecular biomarkers could provide a way of distinguishing oncocytoma from chRCC, which could prevent unnecessary treatment of oncocytoma. Such biomarkers could also be applied to preoperative biopsies such as needle core biopsies, to avoid unnecessary surgery of oncocytoma. Methods: We profiled DNA methylation in fresh-frozen oncocytoma and chRCC tumors and adjacent normal tissue and used machine learning to identify a signature of differentially methylated CpG sites (CpGs) that robustly distinguish oncocytoma from chRCC. Results: Unsupervised clustering of Stanford and pre-existing TCGA RCC data revealed that of all RCC subtypes, oncocytoma is most similar to chRCC. Unexpectedly, however, oncocytoma features more extensive overall abnormal methylation than chRCC. We identified 79 CpGs with large methylation differences between oncocytoma and chRCC. A diagnostic model trained on thirty CpGs could distinguish oncocytoma from chRCC in ten-fold cross validation (area underthe ROC curve (AUC): 0.96 (95% CI: 0.88-1)) and could distinguish TCGA chRCCs from an independent set of oncocytomas from a previous study (AUC=0.87). This signature also separated oncocytoma from other RCC subtypes and normal tissue, revealing it as a standalone diagnostic biomarker for oncocytoma. Conclusions: This CpG signature could be developed as a clinical biomarker to support differential diagnosis of oncocytoma and chRCC in surgical samples. With improved biopsy techniques, this signature could be applied to preoperative biopsies.
dc.description.sponsorshipCRUK
dc.publisherASCO
dc.titleDevelopment of a DNA methylation-based diagnostic signature to distinguish benign oncocytoma form renal cell carcinomaen
dc.typeArticle
prism.endingPage1151
prism.publicationNameJCO Precision Oncologyen
prism.startingPage1141
prism.volume4en
dc.identifier.doi10.17863/CAM.58381
dcterms.dateAccepted2020-07-10en
rioxxterms.versionofrecord10.1200/PO.20.00015en
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2020-07-10en
dc.contributor.orcidStewart, Grant [0000-0003-3188-9140]
dc.identifier.eissn2473-4284
rioxxterms.typeJournal Article/Reviewen
cam.issuedOnline2020-09-28en
dc.identifier.urlhttps://ascopubs.org/doi/full/10.1200/PO.20.00015en
rioxxterms.freetoread.startdate2021-03-28


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