Scalable whole-exome sequencing of cell-free DNA reveals high concordance with metastatic tumors

By V. Adalsteinsson, Gavin Ha, S. Freeman, A. Choudhury, Daniel G. Stover, Heather A. Parsons, G. Gydush, S. Reed, D. Rotem, Justin Rhoades and 47 more. Nature Communications, 2017

879 citations recorded by the source corpus.

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. Identifying the mutational landscape of tumours from cell-free DNA in the blood could help diagnostics in cancer. Here, the authors present ichorCNA, software that quantifies tumour content in cell free DNA, and they demonstrate that cell-free DNA whole-exome sequencing is concordant with metastatic tumour whole-exome sequencing.

Subfields: Cancer Research, Molecular Biology, Pathology and Forensic Medicine

View Paper: https://www.semanticscholar.org/paper/5e1c6059d4f553293dddff19f3c873a5596ad016

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

In Molecular Biology

Citations in the corpus

Genomic and Functional Approaches to Understanding Cancer Aneuploidy (2018, background): “Subclonal analysis was performed using IchorCNA (Adalsteinsson et al., 2017).”
Early detection of cancer (2022, positive): “Analysis of ctDNA has shownpromise for personalizedmutation profiling and monitoring of patients with advanced cancers (58, 60), inwhom ctDNA levels are relatively high.”