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

Circulating Tumor Cells Heterogeneity Melanoma Tumor

Journal

EMBO molecular medicine

ISSN: 1757-4684

Titre abrégé: EMBO Mol Med

Pays: Germany

ID NLM: 101487380

Informations de publication

Date de publication:
19 Jun 2024

Historique:

received: 12 09 2023

accepted: 14 05 2024

revised: 03 05 2024

medline: 20 6 2024

pubmed: 20 6 2024

entrez: 19 6 2024

Statut: aheadofprint

Résumé

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.

Identifiants

DOI: 10.1038/s44321-024-00082-6 PMID: 38898234

pubmed: 38898234

doi: 10.1038/s44321-024-00082-6

pii: 10.1038/s44321-024-00082-6

doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Subventions

Organisme : Deutsche Krebshilfe (German Cancer Aid)

ID : 70114705

Organisme : EC | ERC | HORIZON EUROPE European Research Council (ERC)

ID : 834974

Organisme : Bundesministerium für Bildung und Forschung (BMBF)

ID : 031B0843D

Organisme : Institut National de la Santé et de la Recherche Médicale (Inserm)

ID : Plan Cancer 2014-2019

Informations de copyright

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