20 miliardi di euro l’anno: i costi per il cancro in Italia – Prevenzione attiva, la vera arma vincente
Entitled “Cell-free DNA analysis in healthy individuals by next-generation sequencing: a proof of concept and technical validation study”, was published on Cell Death & Disease – Nature – 2019 – Impact Factor 6.304. Our study investigates the technical feasibility of cell-free DNA (cfDNA) analysis in clinically healthy individuals. It aims to address current challenges for applying liquid biopsy as a clinical tool for early cancer detection. The application of liquid biopsy in clinical settings is mainly confined to monitoring the emergence of resistance to targeted therapy in advanced cancer patients. Much effort is currently being placed towards applying liquid biopsy for early cancer detection. However, technical studies evaluating the feasibility of cfDNA analysis in healthy individuals are missing. We examined the performance of an ultra-sensitive next-generation sequencing liquid biopsy assay in a cohort of 114 individuals clinically healthy at blood collection, as well as 63 patients with diagnosed breast or lung cancer. We assessed the feasibility of implementing our screening method in healthy donors by comparing pre-analytical and analytical variables in healthy and cancer donors.
We further validated the specificity of our assay by looking at the mutational status concordance of matched tissue and liquid biopsy in cancer donors. We then selected 55 healthy donors that were followed up for 1-10 years and looked for genetic alterations in cancer-associated hotspots, comparing individuals that did not develop any tumor during follow-up time to patients that developed either a benign neoplasm or cancer. In conclusion, we have established a rapid and reliable liquid biopsy workflow that allowed us to study genomic alterations with a limit of detection as low as 0.04% of variant allelic frequency in healthy individuals. Affiliation: Institute of Pathology, University Hospital Basel, Switzerland; Department of Medical Surgery, University of Trieste, Italy; Cancer Metastasis Laboratory, University of Basel, Switzerland; Memorial Sloan Kettering Cancer Center, New York USA; BIOSCIENCE INSTITUTE, San Marino; Department of Biomedicine, University of Rome, Italy; Novartis Institutes, Biomedical Research, Basel, Switzerland.
