- Court, Colin M;
- Hou, Shuang;
- Liu, Lian;
- Winograd, Paul;
- DiPardo, Benjamin J;
- Liu, Sean X;
- Chen, Pin-Jung;
- Zhu, Yazhen;
- Smalley, Matthew;
- Zhang, Ryan;
- Sadeghi, Saeed;
- Finn, Richard S;
- Kaldas, Fady M;
- Busuttil, Ronald W;
- Zhou, Xianghong J;
- Tseng, Hsian-Rong;
- Tomlinson, James S;
- Graeber, Thomas G;
- Agopian, Vatche G
Somatic copy number alterations (SCNAs) are important genetic drivers of many cancers. We investigated the feasibility of obtaining SCNA profiles from circulating tumor cells (CTCs) as a molecular liquid biopsy for hepatocellular carcinoma (HCC). CTCs from ten HCC patients underwent SCNA profiling. The Cancer Genome Atlas (TCGA) SCNA data were used to develop a cancer origin classification model, which was then evaluated for classifying 44 CTCs from multiple cancer types. 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 SCNAs in previously reported HCC regions such as 8q amplifications and 17p deletions. SCNA profiling revealed that CTCs share a median of 80% concordance with the primary tumor. CTCs had SCNAs not seen in the primary tumor, some with prognostic implications. Using a SCNA profiling model, the tissue of origin was correctly identified for 32/44 (73%) CTCs from 12/16 (75%) patients with different cancer types.