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

Nat Commun 2017 11 6;8(1):1324. Epub 2017 Nov 6.

Eli and Edythe L. Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, 02142, MA, USA.

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.

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-017-00965-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5673918PMC
November 2017
14 Citations
10.742 Impact Factor

Publication Analysis

Top Keywords

whole-exome sequencing
20
tumor content
8
cfdna
8
high concordance
8
tumor biopsies
8
patients ≥10%
8
cell-free dna
8
cfdna tumor
8
concordance cfdna
8
sequencing cell-free
8
sequencing
6
tumor
6
patients
5
methods identify
4
breast cancers
4
prostate breast
4
summary provide
4
tested sample
4
sample patient
4
metastatic prostate
4

Similar Publications