Comprehensive NGS Panel Validation for the Identification of Actionable Alterations in Adult Solid Tumors

Abstract

The increasing identification of driver oncogenic alterations and progress of targeted therapies addresses the need of comprehensive alternatives to standard molecular methods. The translation into clinical practice of next-generation sequencing (NGS) panels is actually challenged by the compliance of high quality standards for clinical accreditation. Herein, we present the analytical and clinical feasibility study of a hybridization capture-based NGS panel (Action OncoKitDx) for the analysis of somatic mutations, copy number variants (CNVs), fusions, pharmacogenetic SNPs and Microsatellite Instability (MSI) determination in formalin-fixed paraffin-embedded (FFPE) tumor samples. A total of 64 samples were submitted to extensive analytical validation for the identification of previously known variants. An additional set of 166 tumor and patient-matched normal samples were sequenced to assess the clinical utility of the assay across different tumor types. The panel demonstrated good specificity, sensitivity, reproducibility, and repeatability for the identification of all biomarkers analyzed and the 5% limit of detection set was validated. Among the clinical cohorts, the assay revealed pathogenic genomic alterations in 97% of patient cases, and in 82.7%, at least one clinically relevant variant was detected. The validation of accuracy and robustness of this assay supports the Action OncoKitDx’s utility in adult solid tumors.

Is there some predictive factors for isolated brain PROgression in patients with CErebral metastatic MElanoma after stereotactic brain radiotherapy ? PROCEME

“…It is needed to demonstrate the appearance of secondary mutations during the course of the disease. Ideally, biopsies should be taken from the organ undergoing progression, in this case the brain, and sequencing analyses performed using Next Generation Sequencing (NGS) [23].…”

Is there some predictive factors for isolated brain PROgression in patients with CErebral metastatic MElanoma after treatment with stereotactic brain radiotherapy ? a retrospective, single-center study. PROCEME

“…It is needed to demonstrate the appearance of secondary mutations during the course of the disease. Ideally, biopsies should be taken from the organ undergoing progression, in this case the brain, and sequencing analyses performed using Next Generation Sequencing (NGS) [22].…”

Next generation sequencing for personalized therapy: About a class III BRAF N581K mutation associated to NRAS Q61L mutation in malignant melanoma: Case report

“…The aim of this study was not to evaluate the efficiency of the target therapy, but the feasibility and promotion of their method based on sequencing, for individualized approach, called “precision medicine”. Paula Martinez et al [ 25 ] present their panel of new generation sequencing, OncoKitDx, which could be used in solid tumors with a specificity over 99,9% and a sensitivity of 100% with 5% limit of detection.…”