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

doi:10.1038/s41698-020-0123-0

Somatic copy number profiling from hepatocellular carcinoma circulating tumor cells

NPJ Precis Oncol. 2020 Jul 2:4:16. doi: 10.1038/s41698-020-0123-0. eCollection 2020.

Authors

Colin M Court^{1

2

3}, Shuang Hou¹, Lian Liu⁴, Paul Winograd^{1

2}, Benjamin J DiPardo^{1

2}, Sean X Liu⁵, Pin-Jung Chen⁵, Yazhen Zhu⁵, Matthew Smalley⁵, Ryan Zhang⁵, Saeed Sadeghi⁶, Richard S Finn⁶, Fady M Kaldas¹, Ronald W Busuttil^{1

7}, Xianghong J Zhou⁸, Hsian-Rong Tseng^{5

7

9}, James S Tomlinson^{1

2

9}, Thomas G Graeber^{3

5

7

9}, Vatche G Agopian^{1

9}

Affiliations

¹ Department of Surgery, University of California, Los Angeles, Los Angeles, CA USA.
² Department of Surgery, Veteran's Health Administration, Greater Los Angeles, Los Angeles, CA USA.
³ Department of Molecular, Cellular, and Integrative Physiology, University of California, Los Angeles, Los Angeles, CA USA.
⁴ PacGenomics, llc, Los Angeles, CA USA.
⁵ Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA USA.
⁶ Department of Medicine, Division of Hematology/Oncology, University of California, Los Angeles, Los Angeles, CA USA.
⁷ California NanoSystems Institute, University of California, Los Angeles, Los Angeles, CA USA.
⁸ Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA USA.
⁹ Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA USA.

Abstract

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.

Keywords: Molecular medicine; Prognostic markers.

Abstract

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