Validation and clinical application of a targeted next-generation sequencing gene panel for solid and hematologic malignancies

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  • dc.contributor.author Prieto-Potin, Iván
  • dc.contributor.author Carvajal, Nerea
  • dc.contributor.author Plaza-Sánchez, Jenifer
  • dc.contributor.author Manso, Rebeca
  • dc.contributor.author Aúz-Alexandre, Carmen Laura
  • dc.contributor.author Chamizo, Cristina
  • dc.contributor.author Zazo, Sandra
  • dc.contributor.author López-Sánchez, Almudena
  • dc.contributor.author Rodríguez-Pinilla, Socorro María
  • dc.contributor.author Camacho Díaz, Laura
  • dc.contributor.author Longarón Rozalen, Raquel
  • dc.contributor.author Bellosillo Paricio, Beatriz
  • dc.contributor.author Somoza, Rosa
  • dc.contributor.author Hernández-Losa, Javier
  • dc.contributor.author Fernández-Soria, Víctor Manuel
  • dc.contributor.author Ramos-Ruiz, Ricardo
  • dc.contributor.author Cristóbal, Ion
  • dc.contributor.author García-Foncillas, Jesús
  • dc.contributor.author Rojo, Federico
  • dc.date.accessioned 2022-01-28T08:01:04Z
  • dc.date.available 2022-01-28T08:01:04Z
  • dc.date.issued 2020
  • dc.description.abstract Background: Next-generation sequencing (NGS) is a high-throughput technology that has become widely integrated in molecular diagnostics laboratories. Among the large diversity of NGS-based panels, the Trusight Tumor 26 (TsT26) enables the detection of low-frequency variants across 26 genes using the MiSeq platform. Methods: We describe the inter-laboratory validation and subsequent clinical application of the panel in 399 patients presenting a range of tumor types, including gastrointestinal (GI, 29%), hematologic (18%), lung (13%), gynecological and breast (8% each), among others. Results: The panel is highly accurate with a test sensitivity of 92%, and demonstrated high specificity and positive predictive values (95% and 96%, respectively). Sequencing testing was successful in two-thirds of patients, while the remaining third failed due to unsuccessful quality-control filtering. Most detected variants were observed in the TP53 (28%), KRAS (16%), APC (10%) and PIK3CA (8%) genes. Overall, 372 variants were identified, primarily distributed as missense (81%), stop gain (9%) and frameshift (7%) altered sequences and mostly reported as pathogenic (78%) and variants of uncertain significance (19%). Only 14% of patients received targeted treatment based on the variant determined by the panel. The variants most frequently observed in GI and lung tumors were: KRAS c.35G > A (p.G12D), c.35G > T (p.G12V) and c.34G > T (p.G12C). Conclusions: Prior panel validation allowed its use in the laboratory daily practice by providing several relevant and potentially targetable variants across multiple tumors. However, this study is limited by high sample inadequacy rate, raising doubts as to continuity in the clinical setting.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Prieto-Potin I, Carvajal N, Plaza-Sánchez J, Manso R, Aúz-Alexandre CL, Chamizo C, et al. Validation and clinical application of a targeted next-generation sequencing gene panel for solid and hematologic malignancies. PeerJ. 2020 Oct 6; 8: e10069. DOI: 10.7717/peerj.10069
  • dc.identifier.doi http://dx.doi.org/10.7717/peerj.10069
  • dc.identifier.issn 2167-8359
  • dc.identifier.uri http://hdl.handle.net/10230/52348
  • dc.language.iso eng
  • dc.publisher PeerJ Inc.
  • dc.rights Copyright © 2020 Prieto-Potin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, https://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword Cancer
  • dc.subject.keyword Hematological malignancies
  • dc.subject.keyword Next-generation sequencing
  • dc.subject.keyword Solid tumor
  • dc.subject.keyword Validation
  • dc.title Validation and clinical application of a targeted next-generation sequencing gene panel for solid and hematologic malignancies
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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