Scalable whole-exome sequencing of cell-free DNA reveals high concordance with metastatic tumors
Menée à l'aide de données issues du séquençage de l'ADN circulant extrait de 1 439 échantillons sanguins prélevés sur 520 patients atteints d'un cancer métastatique de la prostate ou du sein, cette étude met en évidence une concordance entre les anomalies génétiques observées dans l'ADN circulant et celles observées dans l'ADN tumoral
Whole-exome sequencing of cell-free DNA (cfDNA) could enable comprehensive profiling of tumors from blood but the genome-wide concordance between cfDNA and tumor biopsies is uncertain. Here we report ichorCNA, software that quantifies tumor content in cfDNA from 0.1× coverage whole-genome sequencing data without prior knowledge of tumor mutations. We apply ichorCNA to 1439 blood samples from 520 patients with metastatic prostate or breast cancers. In the earliest tested sample for each patient, 34% of patients have ≥10% tumor-derived cfDNA, sufficient for standard coverage whole-exome sequencing. Using whole-exome sequencing, we validate the concordance of clonal somatic mutations (88%), copy number alterations (80%), mutational signatures, and neoantigens between cfDNA and matched tumor biopsies from 41 patients with ≥10% cfDNA tumor content. In summary, we provide methods to identify patients eligible for comprehensive cfDNA profiling, revealing its applicability to many patients, and demonstrate high concordance of cfDNA and metastatic tumor whole-exome sequencing.
Nature Communications , article en libre accès, 2017