Multifocal clonal evolution characterized using circulating tumour DNA in a case of metastatic breast cancer
A partir de 8 échantillons tumoraux et 9 échantillons plasmatiques prélevés sur une patiente atteinte d'un cancer métastatique du sein ER+ HER2+ (durée de suivi: 1 193 jours), cette étude montre que les niveaux de mutations détectées dans le plasma sont bien le reflet de la hiérarchie clonale déduite du séquençage des biopsies tumorales
Circulating tumour DNA analysis can be used to track tumour burden and analyse cancer genomes non-invasively but the extent to which it represents metastatic heterogeneity is unknown. Here we follow a patient with metastatic ER-positive and HER2-positive breast cancer receiving two lines of targeted therapy over 3 years. We characterize genomic architecture and infer clonal evolution in eight tumour biopsies and nine plasma samples collected over 1,193 days of clinical follow-up using exome and targeted amplicon sequencing. Mutation levels in the plasma samples reflect the clonal hierarchy inferred from sequencing of tumour biopsies. Serial changes in circulating levels of sub-clonal private mutations correlate with different treatment responses between metastatic sites. This comparison of biopsy and plasma samples in a single patient with metastatic breast cancer shows that circulating tumour DNA can allow real-time sampling of multifocal clonal evolution.
Nature Communications , article en libre accès, 2014