PortalPublikationenMutation analysis in individual circulating tumor cells depi...

Mutation analysis in individual circulating tumor cells depicts intratumor heterogeneity in melanoma

Standard

Mutation analysis in individual circulating tumor cells depicts intratumor heterogeneity in melanoma. / Sementsov, Mark; Ott, Leonie; Kött, Julian; Sartori, Alexander; Lusque, Amelie; Degenhardt, Sarah; Segier, Bertille; Heidrich, Isabel; Volkmer, Beate; Greinert, Rüdiger; Mohr, Peter; Simon, Ronald; Stadler, Julia-Christina; Irwin, Darryl; Koch, Claudia; Andreas, Antje; Deitert, Benjamin; Thewes, Verena; Trumpp, Andreas; Schneeweiss, Andreas; Belloum, Yassine; Peine, Sven; Wikman, Harriett; Riethdorf, Sabine; Schneider, Stefan W; Gebhardt, Christoffer; Pantel, Klaus; Keller, Laura.

in: EMBO MOL MED, Jahrgang 16, Nr. 7, 07.2024, S. 1560-1578.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Sementsov, M, Ott, L, Kött, J, Sartori, A, Lusque, A, Degenhardt, S, Segier, B, Heidrich, I, Volkmer, B, Greinert, R, Mohr, P, Simon, R, Stadler, J-C, Irwin, D, Koch, C, Andreas, A, Deitert, B, Thewes, V, Trumpp, A, Schneeweiss, A, Belloum, Y, Peine, S, Wikman, H, Riethdorf, S, Schneider, SW, Gebhardt, C, Pantel, K & Keller, L 2024, 'Mutation analysis in individual circulating tumor cells depicts intratumor heterogeneity in melanoma', EMBO MOL MED, Jg. 16, Nr. 7, S. 1560-1578. https://doi.org/10.1038/s44321-024-00082-6

APA

Sementsov, M., Ott, L., Kött, J., Sartori, A., Lusque, A., Degenhardt, S., Segier, B., Heidrich, I., Volkmer, B., Greinert, R., Mohr, P., Simon, R., Stadler, J-C., Irwin, D., Koch, C., Andreas, A., Deitert, B., Thewes, V., Trumpp, A., ... Keller, L. (2024). Mutation analysis in individual circulating tumor cells depicts intratumor heterogeneity in melanoma. EMBO MOL MED, 16(7), 1560-1578. https://doi.org/10.1038/s44321-024-00082-6

Vancouver

Sementsov M, Ott L, Kött J, Sartori A, Lusque A, Degenhardt S et al. Mutation analysis in individual circulating tumor cells depicts intratumor heterogeneity in melanoma. EMBO MOL MED. 2024 Jul;16(7):1560-1578. https://doi.org/10.1038/s44321-024-00082-6

Bibtex

@article{14ea1beb5ad74074b4182175132bd8b7,
title = "Mutation analysis in individual circulating tumor cells depicts intratumor heterogeneity in melanoma",
abstract = "Circulating tumor DNA (ctDNA) is the cornerstone of liquid biopsy diagnostics, revealing clinically relevant genomic aberrations from blood of cancer patients. Genomic analysis of single circulating tumor cells (CTCs) could provide additional insights into intra-patient heterogeneity, but it requires whole-genome amplification (WGA) of DNA, which might introduce bias. Here, we describe a novel approach based on mass spectrometry for mutation detection from individual CTCs not requiring WGA and complex bioinformatics pipelines. After establishment of our protocol on tumor cell line-derived single cells, it was validated on CTCs of 33 metastatic melanoma patients and the mutations were compared to those obtained from tumor tissue and ctDNA. Although concordance with tumor tissue was superior for ctDNA over CTC analysis, a larger number of mutations were found within CTCs compared to ctDNA (p = 0.039), including mutations in melanoma driver genes, or those associated with resistance to therapy or metastasis. Thus, our results demonstrate proof-of-principle data that CTC analysis can provide clinically relevant genomic information that is not redundant to tumor tissue or ctDNA analysis.",
keywords = "Humans, Melanoma/genetics, Neoplastic Cells, Circulating/pathology, Circulating Tumor DNA/genetics, Mutation, DNA Mutational Analysis, Cell Line, Tumor, Genetic Heterogeneity, Mass Spectrometry, Female, Male",
author = "Mark Sementsov and Leonie Ott and Julian K{\"o}tt and Alexander Sartori and Amelie Lusque and Sarah Degenhardt and Bertille Segier and Isabel Heidrich and Beate Volkmer and R{\"u}diger Greinert and Peter Mohr and Ronald Simon and Julia-Christina Stadler and Darryl Irwin and Claudia Koch and Antje Andreas and Benjamin Deitert and Verena Thewes and Andreas Trumpp and Andreas Schneeweiss and Yassine Belloum and Sven Peine and Harriett Wikman and Sabine Riethdorf and Schneider, {Stefan W} and Christoffer Gebhardt and Klaus Pantel and Laura Keller",
note = "{\textcopyright} 2024. The Author(s).",
year = "2024",
month = jul,
doi = "10.1038/s44321-024-00082-6",
language = "English",
volume = "16",
pages = "1560--1578",
journal = "EMBO MOL MED",
issn = "1757-4676",
publisher = "Wiley-Blackwell",
number = "7",

}

RIS

TY - JOUR

T1 - Mutation analysis in individual circulating tumor cells depicts intratumor heterogeneity in melanoma

AU - Sementsov, Mark

AU - Ott, Leonie

AU - Kött, Julian

AU - Sartori, Alexander

AU - Lusque, Amelie

AU - Degenhardt, Sarah

AU - Segier, Bertille

AU - Heidrich, Isabel

AU - Volkmer, Beate

AU - Greinert, Rüdiger

AU - Mohr, Peter

AU - Simon, Ronald

AU - Stadler, Julia-Christina

AU - Irwin, Darryl

AU - Koch, Claudia

AU - Andreas, Antje

AU - Deitert, Benjamin

AU - Thewes, Verena

AU - Trumpp, Andreas

AU - Schneeweiss, Andreas

AU - Belloum, Yassine

AU - Peine, Sven

AU - Wikman, Harriett

AU - Riethdorf, Sabine

AU - Schneider, Stefan W

AU - Gebhardt, Christoffer

AU - Pantel, Klaus

AU - Keller, Laura

N1 - © 2024. The Author(s).

PY - 2024/7

Y1 - 2024/7

N2 - Circulating tumor DNA (ctDNA) is the cornerstone of liquid biopsy diagnostics, revealing clinically relevant genomic aberrations from blood of cancer patients. Genomic analysis of single circulating tumor cells (CTCs) could provide additional insights into intra-patient heterogeneity, but it requires whole-genome amplification (WGA) of DNA, which might introduce bias. Here, we describe a novel approach based on mass spectrometry for mutation detection from individual CTCs not requiring WGA and complex bioinformatics pipelines. After establishment of our protocol on tumor cell line-derived single cells, it was validated on CTCs of 33 metastatic melanoma patients and the mutations were compared to those obtained from tumor tissue and ctDNA. Although concordance with tumor tissue was superior for ctDNA over CTC analysis, a larger number of mutations were found within CTCs compared to ctDNA (p = 0.039), including mutations in melanoma driver genes, or those associated with resistance to therapy or metastasis. Thus, our results demonstrate proof-of-principle data that CTC analysis can provide clinically relevant genomic information that is not redundant to tumor tissue or ctDNA analysis.

AB - Circulating tumor DNA (ctDNA) is the cornerstone of liquid biopsy diagnostics, revealing clinically relevant genomic aberrations from blood of cancer patients. Genomic analysis of single circulating tumor cells (CTCs) could provide additional insights into intra-patient heterogeneity, but it requires whole-genome amplification (WGA) of DNA, which might introduce bias. Here, we describe a novel approach based on mass spectrometry for mutation detection from individual CTCs not requiring WGA and complex bioinformatics pipelines. After establishment of our protocol on tumor cell line-derived single cells, it was validated on CTCs of 33 metastatic melanoma patients and the mutations were compared to those obtained from tumor tissue and ctDNA. Although concordance with tumor tissue was superior for ctDNA over CTC analysis, a larger number of mutations were found within CTCs compared to ctDNA (p = 0.039), including mutations in melanoma driver genes, or those associated with resistance to therapy or metastasis. Thus, our results demonstrate proof-of-principle data that CTC analysis can provide clinically relevant genomic information that is not redundant to tumor tissue or ctDNA analysis.

KW - Humans

KW - Melanoma/genetics

KW - Neoplastic Cells, Circulating/pathology

KW - Circulating Tumor DNA/genetics

KW - Mutation

KW - DNA Mutational Analysis

KW - Cell Line, Tumor

KW - Genetic Heterogeneity

KW - Mass Spectrometry

KW - Female

KW - Male

U2 - 10.1038/s44321-024-00082-6

DO - 10.1038/s44321-024-00082-6

M3 - SCORING: Journal article

C2 - 38898234

VL - 16

SP - 1560

EP - 1578

JO - EMBO MOL MED

JF - EMBO MOL MED

SN - 1757-4676

IS - 7

ER -