Clinical Application of Circulating Tumor Cells and Circulating Tumor DNA in Uveal Melanoma

Aaron Beasley, Timothy Isaacs, Muhammad A. Khattak, Ames B. Freeman, Richard Allcock, Fred K. Chen, Michelle R. Pereira, Kyle Yau, Jaqueline Bentel, Tersia Vermeulen, Leslie Calapre, Michael Millward, Melanie R. Ziman, Elfin S. Gray

Research output: Contribution to journalArticle

Abstract

Purpose To evaluate the feasibility of using circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) for the management of uveal melanoma (UM).

Patients and Methods Low-coverage whole-genome sequencing was used to determine somatic chromosomal copy number alterations (SCNAs) in primary UM tumors, ctDNA, and whole-genome amplified CTCs. CTCs were immunocaptured using an antimelanoma-associated chondroitin sulfate antibody conjugated to magnetic beads and immunostained for melanoma antigen recognised by T cells 1 (MART1)/glycoprotein 100 (gp100)/S100 calcium-binding protein beta (S100 beta). ctDNA was quantified using droplet digital polymerase chain reaction assay for mutations in the GNAQ, GNA11, PLC beta 4, and CYSLTR2 genes.

Results SCNA analysis of CTCs and ctDNA isolated from a patient with metastatic UM showed good concordance with the enucleated primary tumor. In a cohort of 30 patients with primary UM, CTCs were detected in 58% of patients (one to 37 CTCs per 8 mL of blood), whereas only 26% of patients had detectable ctDNA (1.6 to 29 copies/mL). The presence of CTCs or ctDNA was not associated with tumor size or other prognostic markers. However, the frequent detection of CTCs in patients with early-stage UM supports a model in which CTCs can be used to derive tumor-specific SCNA relevant for prognosis. Monitoring of ctDNA after treatment of the primary tumor allowed detection of metastatic disease earlier than F-18-labeled fluorodeoxyglucose positron emission tomography in two patients.

Conclusion The presence of CTCs in localized UM can be used to ascertain prognostic SCNA, whereas ctDNA can be used to monitor patients for early signs of metastatic disease. This study paves the way for the analysis of CTCs and ctDNA as a liquid biopsy that will assist with treatment decisions in patients with UM. (C) 2018 by American Society of Clinical Oncology

Original languageEnglish
Pages (from-to)1-12
Number of pages12
JournalJCO precision oncology
Volume2
DOIs
Publication statusPublished - 17 May 2018

Cite this

Beasley, Aaron ; Isaacs, Timothy ; Khattak, Muhammad A. ; Freeman, Ames B. ; Allcock, Richard ; Chen, Fred K. ; Pereira, Michelle R. ; Yau, Kyle ; Bentel, Jaqueline ; Vermeulen, Tersia ; Calapre, Leslie ; Millward, Michael ; Ziman, Melanie R. ; Gray, Elfin S. / Clinical Application of Circulating Tumor Cells and Circulating Tumor DNA in Uveal Melanoma. In: JCO precision oncology. 2018 ; Vol. 2. pp. 1-12.
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abstract = "Purpose To evaluate the feasibility of using circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) for the management of uveal melanoma (UM).Patients and Methods Low-coverage whole-genome sequencing was used to determine somatic chromosomal copy number alterations (SCNAs) in primary UM tumors, ctDNA, and whole-genome amplified CTCs. CTCs were immunocaptured using an antimelanoma-associated chondroitin sulfate antibody conjugated to magnetic beads and immunostained for melanoma antigen recognised by T cells 1 (MART1)/glycoprotein 100 (gp100)/S100 calcium-binding protein beta (S100 beta). ctDNA was quantified using droplet digital polymerase chain reaction assay for mutations in the GNAQ, GNA11, PLC beta 4, and CYSLTR2 genes.Results SCNA analysis of CTCs and ctDNA isolated from a patient with metastatic UM showed good concordance with the enucleated primary tumor. In a cohort of 30 patients with primary UM, CTCs were detected in 58{\%} of patients (one to 37 CTCs per 8 mL of blood), whereas only 26{\%} of patients had detectable ctDNA (1.6 to 29 copies/mL). The presence of CTCs or ctDNA was not associated with tumor size or other prognostic markers. However, the frequent detection of CTCs in patients with early-stage UM supports a model in which CTCs can be used to derive tumor-specific SCNA relevant for prognosis. Monitoring of ctDNA after treatment of the primary tumor allowed detection of metastatic disease earlier than F-18-labeled fluorodeoxyglucose positron emission tomography in two patients.Conclusion The presence of CTCs in localized UM can be used to ascertain prognostic SCNA, whereas ctDNA can be used to monitor patients for early signs of metastatic disease. This study paves the way for the analysis of CTCs and ctDNA as a liquid biopsy that will assist with treatment decisions in patients with UM. (C) 2018 by American Society of Clinical Oncology",
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Clinical Application of Circulating Tumor Cells and Circulating Tumor DNA in Uveal Melanoma. / Beasley, Aaron; Isaacs, Timothy; Khattak, Muhammad A.; Freeman, Ames B.; Allcock, Richard; Chen, Fred K.; Pereira, Michelle R.; Yau, Kyle; Bentel, Jaqueline; Vermeulen, Tersia; Calapre, Leslie; Millward, Michael; Ziman, Melanie R.; Gray, Elfin S.

In: JCO precision oncology, Vol. 2, 17.05.2018, p. 1-12.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Clinical Application of Circulating Tumor Cells and Circulating Tumor DNA in Uveal Melanoma

AU - Beasley, Aaron

AU - Isaacs, Timothy

AU - Khattak, Muhammad A.

AU - Freeman, Ames B.

AU - Allcock, Richard

AU - Chen, Fred K.

AU - Pereira, Michelle R.

AU - Yau, Kyle

AU - Bentel, Jaqueline

AU - Vermeulen, Tersia

AU - Calapre, Leslie

AU - Millward, Michael

AU - Ziman, Melanie R.

AU - Gray, Elfin S.

PY - 2018/5/17

Y1 - 2018/5/17

N2 - Purpose To evaluate the feasibility of using circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) for the management of uveal melanoma (UM).Patients and Methods Low-coverage whole-genome sequencing was used to determine somatic chromosomal copy number alterations (SCNAs) in primary UM tumors, ctDNA, and whole-genome amplified CTCs. CTCs were immunocaptured using an antimelanoma-associated chondroitin sulfate antibody conjugated to magnetic beads and immunostained for melanoma antigen recognised by T cells 1 (MART1)/glycoprotein 100 (gp100)/S100 calcium-binding protein beta (S100 beta). ctDNA was quantified using droplet digital polymerase chain reaction assay for mutations in the GNAQ, GNA11, PLC beta 4, and CYSLTR2 genes.Results SCNA analysis of CTCs and ctDNA isolated from a patient with metastatic UM showed good concordance with the enucleated primary tumor. In a cohort of 30 patients with primary UM, CTCs were detected in 58% of patients (one to 37 CTCs per 8 mL of blood), whereas only 26% of patients had detectable ctDNA (1.6 to 29 copies/mL). The presence of CTCs or ctDNA was not associated with tumor size or other prognostic markers. However, the frequent detection of CTCs in patients with early-stage UM supports a model in which CTCs can be used to derive tumor-specific SCNA relevant for prognosis. Monitoring of ctDNA after treatment of the primary tumor allowed detection of metastatic disease earlier than F-18-labeled fluorodeoxyglucose positron emission tomography in two patients.Conclusion The presence of CTCs in localized UM can be used to ascertain prognostic SCNA, whereas ctDNA can be used to monitor patients for early signs of metastatic disease. This study paves the way for the analysis of CTCs and ctDNA as a liquid biopsy that will assist with treatment decisions in patients with UM. (C) 2018 by American Society of Clinical Oncology

AB - Purpose To evaluate the feasibility of using circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) for the management of uveal melanoma (UM).Patients and Methods Low-coverage whole-genome sequencing was used to determine somatic chromosomal copy number alterations (SCNAs) in primary UM tumors, ctDNA, and whole-genome amplified CTCs. CTCs were immunocaptured using an antimelanoma-associated chondroitin sulfate antibody conjugated to magnetic beads and immunostained for melanoma antigen recognised by T cells 1 (MART1)/glycoprotein 100 (gp100)/S100 calcium-binding protein beta (S100 beta). ctDNA was quantified using droplet digital polymerase chain reaction assay for mutations in the GNAQ, GNA11, PLC beta 4, and CYSLTR2 genes.Results SCNA analysis of CTCs and ctDNA isolated from a patient with metastatic UM showed good concordance with the enucleated primary tumor. In a cohort of 30 patients with primary UM, CTCs were detected in 58% of patients (one to 37 CTCs per 8 mL of blood), whereas only 26% of patients had detectable ctDNA (1.6 to 29 copies/mL). The presence of CTCs or ctDNA was not associated with tumor size or other prognostic markers. However, the frequent detection of CTCs in patients with early-stage UM supports a model in which CTCs can be used to derive tumor-specific SCNA relevant for prognosis. Monitoring of ctDNA after treatment of the primary tumor allowed detection of metastatic disease earlier than F-18-labeled fluorodeoxyglucose positron emission tomography in two patients.Conclusion The presence of CTCs in localized UM can be used to ascertain prognostic SCNA, whereas ctDNA can be used to monitor patients for early signs of metastatic disease. This study paves the way for the analysis of CTCs and ctDNA as a liquid biopsy that will assist with treatment decisions in patients with UM. (C) 2018 by American Society of Clinical Oncology

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U2 - 10.1200/PO.17.00279

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JO - JCO precision oncology

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