Analysis of mutation detection in cell-free DNA in ascites using comprehensive NGS panel.

Abstract

e13029 Background: Ascites is one of complications for patients with malignancies in advanced stage. Detection and characterization of cell-free DNA (cfDNA) from ascites effusions have not yet been studied. Herein, we analysis genomic alterations present in advanced cancer with ascites. Methods: We implemented targeted capture NGS with a panel of 1021 cancer-relevant genes on 85 ascites ctDNA, also on 46 matched plasma and 9 tissue from 85 patients. Results: Among 85 patients with advanced cancer, 42 digest system cancer (DC), 16 gynecologic cancer (GC), 14 non-small cell lung cancer(NSCLC) and 13 other solid tumors included. Overall, 90%(77/85) patients detected somatic mutations, which were identified predominantly in TP53 and KRAS for DC and TP53 for GC. Among NSCLC patients with ascites, nine were treated with EGFR TKI-targeted therapy previously. Mutations lead to the resistance of EGFR-TKI were identified in 55.6% (5/9) cases, including acquired EGFR T790M/C797S and primary BRAF V600E. These indicate ctDNA in ascites can used to guide tumor treatment and monitor of resistance. For the 46 pairs of ascites and plasma samples, actionable variations with on label, off-label, or experimental drugs available, were identified in 61% (n = 28) of ascites effusion samples, whereas plasma was 46% (n = 21). Median number of ascites somatic mutations was 4, while the median number was 3 in plasma samples. Of that, 85% and 61% of plasma ctDNA and ascites cfDNA samples were observed with the highest MAF above 1%. In addition, 63% and 35% of plasma ctDNA and pleural cfDNA samples were observed with the highest MAF above 10%. For the 9 groups of plasma, ascites and tumor tissue samples, at least 1 mutations within tissue was detected in 8 ascites samples and 6 in plasma samples. Conclusions: Our results suggest that cfDNA from ascites is more sensitive than plasma and had higher similarity with the tumor tissues for advanced cancer patients. With higher MAF and detection rate of actionable variations, cfDNA from ascites might provide additional information not detected with plasma cell-free DNA guide more precise cancer treatment.