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

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

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11 Scopus citations

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.

Original language	English (US)
Article number	16
Journal	npj Precision Oncology
Volume	4
Issue number	1
DOIs	https://doi.org/10.1038/s41698-020-0123-0
State	Published - Dec 1 2020

ASJC Scopus subject areas

Oncology
Cancer Research

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Court, C. M., Hou, S., Liu, L., Winograd, P., DiPardo, B. J., Liu, S. X., Chen, P. J., Zhu, Y., Smalley, M., Zhang, R., Sadeghi, S., Finn, R. S., Kaldas, F. M., Busuttil, R. W., Zhou, X. J., Tseng, H. R., Tomlinson, J. S., Graeber, T. G., & Agopian, V. G. (2020). Somatic copy number profiling from hepatocellular carcinoma circulating tumor cells. npj Precision Oncology, 4(1), [16]. https://doi.org/10.1038/s41698-020-0123-0

Court, CM, Hou, S, Liu, L, Winograd, P, DiPardo, BJ, Liu, SX, Chen, PJ, Zhu, Y, Smalley, M, Zhang, R, Sadeghi, S, Finn, RS, Kaldas, FM, Busuttil, RW, Zhou, XJ, Tseng, HR, Tomlinson, JS, Graeber, TG & Agopian, VG 2020, 'Somatic copy number profiling from hepatocellular carcinoma circulating tumor cells', npj Precision Oncology, vol. 4, no. 1, 16. https://doi.org/10.1038/s41698-020-0123-0

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title = "Somatic copy number profiling from hepatocellular carcinoma circulating tumor cells",

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.",

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

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AU - Agopian, Vatche G.

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N2 - 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.

AB - 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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Somatic copy number profiling from hepatocellular carcinoma circulating tumor cells

Abstract

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