Intra-Patient Heterogeneity of Circulating Tumor Cells and Circulating Tumor DNA in Blood of Melanoma Patients

Despite remarkable progress in melanoma therapy, the exceptional heterogeneity of the disease has prevented the development of reliable companion biomarkers for the prediction or monitoring of therapy responses. Here, we show that difficulties in detecting blood-based markers, like circulating tumor...

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Main Authors: Katharina Gorges, Lisa Wiltfang, Tobias M. Gorges, Alexander Sartori, Lina Hildebrandt, Laura Keller, Beate Volkmer, Sven Peine, Anna Babayan, Ingrid Moll, Stefan W. Schneider, Sören Twarock, Peter Mohr, Jens W. Fischer, Klaus Pantel
Format: Article
Language:English
Published: MDPI AG 2019-10-01
Series:Cancers
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Online Access:https://www.mdpi.com/2072-6694/11/11/1685
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author Katharina Gorges
Lisa Wiltfang
Tobias M. Gorges
Alexander Sartori
Lina Hildebrandt
Laura Keller
Beate Volkmer
Sven Peine
Anna Babayan
Ingrid Moll
Stefan W. Schneider
Sören Twarock
Peter Mohr
Jens W. Fischer
Klaus Pantel
author_facet Katharina Gorges
Lisa Wiltfang
Tobias M. Gorges
Alexander Sartori
Lina Hildebrandt
Laura Keller
Beate Volkmer
Sven Peine
Anna Babayan
Ingrid Moll
Stefan W. Schneider
Sören Twarock
Peter Mohr
Jens W. Fischer
Klaus Pantel
author_sort Katharina Gorges
collection DOAJ
description Despite remarkable progress in melanoma therapy, the exceptional heterogeneity of the disease has prevented the development of reliable companion biomarkers for the prediction or monitoring of therapy responses. Here, we show that difficulties in detecting blood-based markers, like circulating tumor cells (CTC), might arise from the translation of the mutational heterogeneity of melanoma cells towards their surface marker expression. We provide a unique method, which enables the molecular characterization of clinically relevant CTC subsets, as well as circulating tumor DNA (ctDNA), from a single blood sample. The study demonstrates the benefit of a combined analysis of ctDNA and CTC counts in melanoma patients, revealing that CTC subsets and ctDNA provide synergistic real-time information on the mutational status, RNA and protein expression of melanoma cells in individual patients, in relation to clinical outcome.
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spelling doaj.art-9f5b29d64a334e11b5a23f66fa44a5792023-08-02T05:13:59ZengMDPI AGCancers2072-66942019-10-011111168510.3390/cancers11111685cancers11111685Intra-Patient Heterogeneity of Circulating Tumor Cells and Circulating Tumor DNA in Blood of Melanoma PatientsKatharina Gorges0Lisa Wiltfang1Tobias M. Gorges2Alexander Sartori3Lina Hildebrandt4Laura Keller5Beate Volkmer6Sven Peine7Anna Babayan8Ingrid Moll9Stefan W. Schneider10Sören Twarock11Peter Mohr12Jens W. Fischer13Klaus Pantel14Institute for Pharmacology and Clinical Pharmacology, University Hospital of the Heinrich-Heine-University, 40225 Düsseldorf, GermanyDepartment of Tumor Biology, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, GermanyDepartment of Tumor Biology, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, GermanyAgena Bioscience GmbH, 22761 Hamburg, GermanyDepartment of Dermatology, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, GermanyDepartment of Tumor Biology, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, GermanyDepartment of Dermatology, Elbe Kliniken, 21614 Buxtehude, GermanyInstitute of Transfusion Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, GermanyDepartment of Tumor Biology, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, GermanyDermatoMed, 22303 Hamburg, GermanyDepartment of Dermatology, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, GermanyInstitute for Pharmacology and Clinical Pharmacology, University Hospital of the Heinrich-Heine-University, 40225 Düsseldorf, GermanyDepartment of Dermatology, Elbe Kliniken, 21614 Buxtehude, GermanyInstitute for Pharmacology and Clinical Pharmacology, University Hospital of the Heinrich-Heine-University, 40225 Düsseldorf, GermanyDepartment of Tumor Biology, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, GermanyDespite remarkable progress in melanoma therapy, the exceptional heterogeneity of the disease has prevented the development of reliable companion biomarkers for the prediction or monitoring of therapy responses. Here, we show that difficulties in detecting blood-based markers, like circulating tumor cells (CTC), might arise from the translation of the mutational heterogeneity of melanoma cells towards their surface marker expression. We provide a unique method, which enables the molecular characterization of clinically relevant CTC subsets, as well as circulating tumor DNA (ctDNA), from a single blood sample. The study demonstrates the benefit of a combined analysis of ctDNA and CTC counts in melanoma patients, revealing that CTC subsets and ctDNA provide synergistic real-time information on the mutational status, RNA and protein expression of melanoma cells in individual patients, in relation to clinical outcome.https://www.mdpi.com/2072-6694/11/11/1685melanomactdnactcliquid biopsy
spellingShingle Katharina Gorges
Lisa Wiltfang
Tobias M. Gorges
Alexander Sartori
Lina Hildebrandt
Laura Keller
Beate Volkmer
Sven Peine
Anna Babayan
Ingrid Moll
Stefan W. Schneider
Sören Twarock
Peter Mohr
Jens W. Fischer
Klaus Pantel
Intra-Patient Heterogeneity of Circulating Tumor Cells and Circulating Tumor DNA in Blood of Melanoma Patients
Cancers
melanoma
ctdna
ctc
liquid biopsy
title Intra-Patient Heterogeneity of Circulating Tumor Cells and Circulating Tumor DNA in Blood of Melanoma Patients
title_full Intra-Patient Heterogeneity of Circulating Tumor Cells and Circulating Tumor DNA in Blood of Melanoma Patients
title_fullStr Intra-Patient Heterogeneity of Circulating Tumor Cells and Circulating Tumor DNA in Blood of Melanoma Patients
title_full_unstemmed Intra-Patient Heterogeneity of Circulating Tumor Cells and Circulating Tumor DNA in Blood of Melanoma Patients
title_short Intra-Patient Heterogeneity of Circulating Tumor Cells and Circulating Tumor DNA in Blood of Melanoma Patients
title_sort intra patient heterogeneity of circulating tumor cells and circulating tumor dna in blood of melanoma patients
topic melanoma
ctdna
ctc
liquid biopsy
url https://www.mdpi.com/2072-6694/11/11/1685
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