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

PeerJ

article

Iván Prieto-Potin¹  Nerea Carvajal¹  Jenifer Plaza-Sánchez¹  Rebeca Manso¹  Carmen Laura Aúz-Alexandre¹  Cristina Chamizo¹  Sandra Zazo¹  Almudena López-Sánchez¹  Socorro María Rodríguez-Pinilla¹  Laura Camacho²  Raquel Longarón²  Beatriz Bellosillo²  Rosa Somoza³  Javier Hernández-Losa³  Víctor Manuel Fernández-Soria⁴  Ricardo Ramos-Ruiz⁴  Ion Cristóbal⁵  Jesús García-Foncillas⁵  Federico Rojo¹ 

[1] Department of Pathology, CIBERONC, UAM, Fundación Jiménez Díaz University Hospital Health Research Institute;Department of Pathology, Hospital Del Mar Medical Research Institute;Department of Pathology, Vall d’Hebron University Hospital;Genomics Unit, Madrid Science Park;Translational Oncology Division, UAM, Fundación Jiménez Díaz University Hospital Health Research Institute

关键词: Next-generation sequencing;    Validation;    Cancer;    Solid tumor;    Hematological malignancies;   

DOI  :  10.7717/peerj.10069

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

BackgroundNext-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.MethodsWe 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.ResultsThe 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 T (p.G12C).ConclusionsPrior 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.

【 授权许可】

CC BY