Clinical utility of targeted RNA sequencing in cancer molecular diagnostics
Menée à partir d'échantillons tissulaires, d'échantillons sanguins et d'échantillons de moelle d'osseuse issus de patients pédiatriques ou adultes atteints d'un cancer, cette étude examine l'utilité clinique de séquençages ciblés de l'ARN pour établir un diagnostic
Molecular diagnostics in oncology uses next-generation sequencing to improve diagnostic precision, prognostic prediction and therapeutic target selection. To date, most approaches have focused on DNA-based sequencing. However, RNA sequencing (RNA-seq) enables superior fusion detection and functional characterization of other alterations including splice site mutations and expression changes. Here we report our prospective, real-world, clinical experience using a single, targeted RNA-seq assay on 2,310 solid, central nervous system and hematopoietic neoplasms from children and adults (range 0–90 years). RNA-seq performed as well as DNA-based diagnostics, with a 4.8% failure rate despite the fact that most samples were formalin fixed and paraffin embedded, and provided valuable molecular data for 87% of patients, including diagnostic alterations that resulted in revised diagnoses and the identification of clinically actionable alterations that led to a change in treatment for patients, including the administration of targeted therapies. Our experience supports the use of RNA-seq as a stand-alone tool for precision clinical diagnostics, minimizing cost, tissue requirement and turnaround time.
Nature Medicine , résumé, 2025