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Abstract Details
Somatic copy number profiling from hepatocellular carcinoma circulating tumor cells
Colin M Court123, Shuang Hou1, Lian Liu4, Paul Winograd12, Benjamin J DiPardo12, Sean X Liu5, Pin-Jung Chen5, Yazhen Zhu5, Matthew Smalley5, Ryan Zhang5, Saeed Sadeghi6, Richard S Finn6, Fady M Kaldas1, Ronald W Busuttil17, Xianghong J Zhou8, Hsian-Rong Tseng579, James S Tomlinson129, Thomas G Graeber3579, Vatche G Agopian19
Author information
1Department of Surgery, University of California, Los Angeles, Los Angeles, CA USA.
2Department of Surgery, Veteran's Health Administration, Greater Los Angeles, Los Angeles, CA USA.
3Department of Molecular, Cellular, and Integrative Physiology, University of California, Los Angeles, Los Angeles, CA USA.
4PacGenomics, llc, Los Angeles, CA USA.
5Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA USA.
6Department of Medicine, Division of Hematology/Oncology, University of California, Los Angeles, Los Angeles, CA USA.
7California NanoSystems Institute, University of California, Los Angeles, Los Angeles, CA USA.
8Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA USA.
9Jonsson 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.