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Somatic copy number profiling from hepatocellular carcinoma circulating tumor cells.

  • Author(s): 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
  • et al.

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.

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