Next-generation sequencing of bile cell-free DNA for the early detection of patients with malignant biliary strictures

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dc.contributor.authorArechederra, María
dc.contributor.authorRullán Iriarte, María
dc.contributor.authorAmat Villegas, Irene
dc.contributor.authorOyón, Daniel
dc.contributor.authorZabalza, Lucía
dc.contributor.authorElizalde, María
dc.contributor.authorLatasa, Maria Ujue
dc.contributor.authorMercado Gutiérrez, María R.
dc.contributor.authorRuiz-Clavijo, Daniel
dc.contributor.authorSaldaña, Cristina
dc.contributor.authorFernández-Urién Sainz, Ignacio
dc.contributor.authorCarrascosa, Juan
dc.contributor.authorJusué, Vanesa
dc.contributor.authorGuerrero Setas, David
dc.contributor.authorZazpe, Cruz
dc.contributor.authorGonzález Borja, Iranzu
dc.contributor.authorSangro, Bruno
dc.contributor.authorHerranz, José M.
dc.contributor.authorPurroy, Ana
dc.contributor.authorGil, Isabel
dc.contributor.authorNelson, Leonard J.
dc.contributor.authorVila, Juan J.
dc.contributor.authorKrawczyk, Marcin
dc.contributor.authorZieniewicz, Krzysztof
dc.contributor.authorPatkowski, Waldemar
dc.contributor.authorMilkiewicz, Piotr
dc.contributor.authorCubero, Francisco Javier
dc.contributor.authorAlkorta Aranburu, Gorka
dc.contributor.authorFernández-Barrena, Maite G.
dc.contributor.authorUrman Fernández, Jesús María
dc.contributor.authorBerasain, Carmen
dc.contributor.authorÁvila, Matías A.
dc.contributor.departmentCiencias de la Saludes_ES
dc.contributor.departmentOsasun Zientziakeu
dc.contributor.funderGobierno de Navarra / Nafarroako Gobernuaes
dc.date.accessioned2022-01-10T11:14:22Z
dc.date.available2022-01-10T11:14:22Z
dc.date.issued2021
dc.description.abstractObjective: despite significant progresses in imaging and pathological evaluation, early differentiation between benign and malignant biliary strictures remains challenging. Endoscopic retrograde cholangiopancreatography (ERCP) is used to investigate biliary strictures, enabling the collection of bile. We tested the diagnostic potential of next-generation sequencing (NGS) mutational analysis of bile cell-free DNA (cfDNA). Design: a prospective cohort of patients with suspicious biliary strictures (n=68) was studied. The performance of initial pathological diagnosis was compared with that of the mutational analysis of bile cfDNA collected at the time of first ERCP using an NGS panel open to clinical laboratory implementation, the Oncomine Pan-Cancer Cell-Free assay. Results: an initial pathological diagnosis classified these strictures as of benign (n=26), indeterminate (n=9) or malignant (n=33) origin. Sensitivity and specificity of this diagnosis were 60% and 100%, respectively, as on follow-up 14 of the 26 and eight of the nine initially benign or indeterminate strictures resulted malignant. Sensitivity and specificity for malignancy of our NGS assay, herein named Bilemut, were 96.4% and 69.2%, respectively. Importantly, one of the four Bilemut false positives developed pancreatic cancer after extended follow-up. Remarkably, the sensitivity for malignancy of Bilemut was 100% in patients with an initial diagnosis of benign or indeterminate strictures. Analysis of 30 paired bile and tissue samples also demonstrated the superior performance of Bilemut. Conclusion: implementation of Bilemut at the initial diagnostic stage for biliary strictures can significantly improve detection of malignancy, reduce delays in the clinical management of patients and assist in selecting patients for targeted therapies.en
dc.description.sponsorshipFunding: we thank the financial support of CIBERehd; grants PI16/01126 and PI19/00163 from Instituto de Salud Carlos III (ISCIII) cofinanced by ’Fondo Europeo de Desarrollo Regional’ (FEDER) ’Una manera de hacer Europa’; grants 58/2017 and 55/2018 from Gobierno de Navarra Salud; grant 0011-1411-2020-000010 from AGATA Strategic Project from Gobierno de Navarra; grant 2020/101 from Euroregion Nouvelle Aquitaine-Euskadi-Navarra; Fundación Eugenio Rodríguez Pascual; Fundación Mario Losantos, Fundación M Torres; grant 2018/117 from AMMF, the Cholangiocarcinoma Charity; the COST Action CA181122 Euro-cholangio-Net; POSTD18014AREC postdoctoral fellowship from AECC to MA; and Ramón y Cajal Program contracts RYC-2014-15242 and RYC-2018-024475-1 to FJC and MGFB.en
dc.format.extent22 p.
dc.format.mimetypeapplication/pdfen
dc.identifier.doi10.1136/gutjnl-2021-325178
dc.identifier.issn0017-5749
dc.identifier.urihttps://academica-e.unavarra.es/handle/2454/41677
dc.language.isoengen
dc.publisherBMJ Publishing Group
dc.relation.ispartofGut. 2021; 0:1–11
dc.relation.publisherversionhttp://doi.org/10.1136/gutjnl-2021-325178
dc.rights© Author(s). Creative Commons Attribution-NonCommercial License 4.0en
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttps://creativecommons.org/licenses/by-nc/4.0/
dc.subjectBiliary stricturesen
dc.subjectCholangiocarcinomaen
dc.subjectDiagnostic and therapeutic endoscopyen
dc.subjectMutation screeningen
dc.subjectPancreatic tumoursen
dc.titleNext-generation sequencing of bile cell-free DNA for the early detection of patients with malignant biliary stricturesen
dc.typeinfo:eu-repo/semantics/article
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dspace.entity.typePublication
relation.isAuthorOfPublication62121697-1430-4bf6-9314-fc56c7808292
relation.isAuthorOfPublicationee6367c6-ca22-49b5-a39e-470306c950a4
relation.isAuthorOfPublication2b63819b-ccbc-48c7-9a99-fcf089f17a20
relation.isAuthorOfPublication.latestForDiscovery62121697-1430-4bf6-9314-fc56c7808292

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