Somatic copy number profiling of hepatocellular carcinoma circulating tumor cells.

Abstract

290 Background: Copy number variations (CNVs) have shown prognostic and predictive utility in hepatocellular carcinoma (HCC) but their use from percutaneous biopsies is limited due to HCC’s significant tumor heterogeneity. We investigated the feasibility of obtaining CNV profiles from circulating tumor cells (CTCs) as a liquid biopsy for HCC. Methods: Using a microfluidic HCC-specific CTC assay, CTCs were isolated from 10 patients with HCC and low-resolution (~0.01x) whole genome sequencing performed to establish CNV profiles. Primary tumor, peritumoral liver, and germline DNA was sequenced for comparison. Results: Sequencing of 18 CTC samples (median 4 CTCs/sample) from 10 HCC patients using a low-resolution whole genome sequencing strategy (median 0.88 million reads/sample) revealed frequent copy number changes in previously reported HCC regions such as 8q amplifications and 17p deletions. Analysis of CNV profiles revealed that CTCs share a median of 80% concordance with the primary tumor and that CTCs clustered with their respective primary tumor for 9/10 samples. Sequencing of 7 different CTC samples from a single patient established the reproducibility of the assay. CTCs also demonstrated CNVs not seen in the primary tumor, some with prognostic implications. Conclusions: CNV profiling of HCC-CTCs is feasible and accurately recapitulates CNVs seen in the primary tumor. The use of CTC-derived genetic profiles as clinically relevant surrogates of HCC tumors demonstrates potential and should be explored further. [Table: see text]