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Whole-exome sequencing studies of parathyroid carcinomas reveal novel PRUNE2 mutations, distinctive mutational spectra related to APOBEC-catalyzed DNA mutagenesis and mutational enrichment in kinases associated with cell migration and invasion

2015-02Artigo científico Acesso aberto
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dc.contributor.authorYu, Willie
dc.contributor.authorMcPherson, John R.
dc.contributor.authorStevenson, Mark
dc.contributor.authorVan Eijk, Ronald
dc.contributor.authorHeng, Hong Lee
dc.contributor.authorNewey, Paul
dc.contributor.authorGan, Anna
dc.contributor.authorRuano, Dina
dc.contributor.authorHuang, Dachuan
dc.contributor.authorPoon, Song Ling
dc.contributor.authorOng, Choon Kiat
dc.contributor.authorVan Wezel, Tom
dc.contributor.authorCavaco, Branca
dc.contributor.authorRozen, Steven G.
dc.contributor.authorTan, Patrick
dc.contributor.authorTeh, Bin T.
dc.contributor.authorThakker, Rajesh V.
dc.contributor.authorMorreau, Hans
dc.contributor.institutionCentro de Estudos de Doenças Crónicas (CEDOC)
dc.contributor.institutionNOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
dc.contributor.pblEndocrine Society
dc.date.accessioned2023-05-11T22:08:06Z
dc.date.available2023-05-11T22:08:06Z
dc.date.issued2015-02
dc.description.abstractContext: Cell division cycle 73 (CDC73), encoding the protein parafibromin, is the most prevalent mutated gene in familial and sporadic parathyroid carcinoma (PC). Objective: To identify additional genetic abnormalities in PCs. Design: Whole-exome sequencingwas performedusing DNA from seven pairs of matched PCs and one triplet containing double primary tumor and normal leukocyte. Somatic variants were confirmed using Sanger sequencing and recurrently mutated genes were assessed in 13 additional PCs as well as 40 parathyroid adenomas (PA). Results: PC had an average of 51 somatic variants/tumor (range 3-176) with approximately 58% of variants occurring as nonsynonymous single nucleotide variants. The importance of CDC73 in PC is reinforced with a remarkable preferential amplification of the mutant CDC73 allele. Furthermore, recurrent germ line and somatic mutations in prune homolog 2 [Drosophila] (PRUNE2) were found in PC and computationally predicted to be deleterious; in addition, recurrent mutations in kinase genes related to cell migration and invasion were found. PRUNE2 showed recurrent mutations in 18% (4/22) of PCs with additional screening in 40 PAs revealing only one rare missense polymorphism (Asp1677Asn). For the first time, the mutational signature associated with apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC)-catalyzed cytosine-to-uracil deamination is found in a subset of PC. Conclusion: This study outlines the genetic landscape of PC and attempts to characterize the mutational processes shaping the PC genome.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent553117
dc.identifier.doi10.1210/jc.2014-3238
dc.identifier.issn0021-972X
dc.identifier.otherPURE: 4111355
dc.identifier.otherPURE UUID: 16c6a86b-13b6-43f6-95e0-17b4a6e290bc
dc.identifier.otherScopus: 84927566019
dc.identifier.otherPubMed: 25387265
dc.identifier.otherWOS: 000353350900031
dc.identifier.urihttp://hdl.handle.net/10362/152630
dc.identifier.urlhttps://www.scopus.com/pages/publications/84927566019
dc.language.isoeng
dc.peerreviewedyes
dc.subjectEndocrinology, Diabetes and Metabolism
dc.subjectBiochemistry
dc.subjectEndocrinology
dc.subjectClinical Biochemistry
dc.subjectBiochemistry, medical
dc.subjectSDG 3 - Good Health and Well-being
dc.titleWhole-exome sequencing studies of parathyroid carcinomas reveal novel PRUNE2 mutations, distinctive mutational spectra related to APOBEC-catalyzed DNA mutagenesis and mutational enrichment in kinases associated with cell migration and invasionen
dc.typejournal article
degois.publication.firstPageE360
degois.publication.issue2
degois.publication.lastPageE364
degois.publication.titleJournal of Clinical Endocrinology & Metabolism
degois.publication.volume100
dspace.entity.typePublication
rcaap.rightsopenAccess

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