Early Cancer Detection in Li-Fraumeni Syndrome with Cell-Free DNA
Menée à partir notamment de 193 échantillons sanguins prélevés sur 89 patients présentant un syndrome de Li Fraumeni, cette étude met en évidence l'intérêt d'une approche multimodale, reposant sur l'analyse du génome, du méthylome et du fragmentome à partir de l'ADN libre circulant, pour détecter précocement un cancer
People with Li-Fraumeni syndrome harbor a germline pathogenic variant in the TP53 tumor suppressor gene; face a near 100% lifetime risk of cancer; and routinely undergo intensive surveillance protocols. Liquid biopsy has become an attractive tool for a range of clinical applications, including early cancer detection. Here, we provide a proof-of-principle for a multi-modal liquid biopsy assay that integrates a targeted gene panel, shallow whole genome, and cell-free methylated DNA immunoprecipitation sequencing for the early detection of cancer in a longitudinal cohort of 89 Li-Fraumeni syndrome patients. Multi-modal analysis increased our detection rate in patients with an active cancer diagnosis over uni-modal analysis; and was able to detect cancer-associated signal in carriers prior to diagnosis with conventional screening (PPV = 67.6%, NPV = 96.5%). While adoption of liquid biopsy into current surveillance will require further clinical validation, this study provides a framework for individuals with Li-Fraumeni syndrome.
Cancer Discovery , article en libre accès, 2022