Concordance of Genomic Alterations between Circulating Tumor DNA and Matched Tumor Tissue in Chinese Patients with...

Circulating tumor DNA (ctDNA) served as a noninvasive method with less side effects using peripheral blood. Given the studies on concordance rate between liquid and solid biopsies in Chinese breast cancer (BC) patients were limited, we sought to examine the concordance rate of different kinds of genomic alterations between paired tissue biopsies and ctDNA samples in Chinese BC cohorts.

In this study, we analyzed the genomic alteration profiles of 81 solid BC samples and 41 liquid BC samples. The concordance across 136 genes was evaluated.

The median mutation counts per sample in 41 ctDNA samples was higher than the median in 81 tissue samples (p=0.0254; Wilcoxon rank sum test). For mutation at the protein-coding level, 39.0% (16/41) samples had at least one concordant mutation in two biopsies. 20.0% tissue-derived mutations could be detected via ctDNA-based sequencing, whereas 11.7% ctDNA-derived mutations could be found in paired tissues. At gene amplification level, the overall concordant rate was 68.3% (28/41). The concordant rate at gene level for each patient ranged from 83.8% (114/136) to 99.3% (135/136). And, the mean level of variant allele frequency (VAF) for concordant mutations in ctDNA was statistically higher than that for the discordant ones (p < 0.001; Wilcoxon rank sum test). Across five representative genes, the overall sensitivity and specificity were 49.0% and 85.9%, respectively.

Our results indicated that ctDNA could provide complementary information on genetic characterizations in detecting single nucleotide variants (SNVs) and insertions and deletions (InDels).