Somatic copy number profiling from hepatocellular carcinoma circulating tumor cells

Colin M. Court, Shuang Hou, Lian Liu, Paul Winograd, Benjamin J. DiPardo, Sean X. Liu, Pin Jung Chen, Yazhen Zhu, Matthew Smalley, Ryan Zhang, Saeed Sadeghi, Richard S. Finn, Fady M. Kaldas, Ronald W. Busuttil, Xianghong J. Zhou, Hsian Rong Tseng, James S. Tomlinson, Thomas G. Graeber, Vatche G. Agopian

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


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.

Original languageEnglish (US)
Article number16
Journalnpj Precision Oncology
Issue number1
StatePublished - Dec 1 2020

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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