Accurate identification of somatic mutations is fundamental for cancer research. While their detection traditionally relies on DNA sequencing with matched tumor-normal samples, RNA sequencing (RNA-seq) offers distinct advantages by restricting analysis to expressed mutations with greater therapeutic potential. However, most RNA-seq datasets, particularly in clinical practice, lack matched normal samples, making reliable discrimination between somatic and germline variants a major challenge. As a result, RNA-based somatic mutation discovery in tumor-only settings remains inconsistent, with substantial variability across existing variant-calling pipelines and no established standard.
PhD student Annelien Morlion presents her recent work on plasma cell-free RNA profiles in cancer type and patient-specific changes.
Background: Circulating nucleic acids in blood plasma form an attractive resource to study human health and disease. While the presence of extracellular RNAs in plasma has been firmly established, their origin and clinical utility for management of cancer patients is less understood.
Methods: In this study, we applied messenger RNA capture sequencing of blood plasma cell-free RNA from 266 cancer patients and cancer-free controls (discovery n=208, 25 cancer types; validation n=58, 3 types).