ArticleCancers2021
The C-Circle Biomarker Is Secreted by Alternative-Lengthening-of-Telomeres Positive Cancer Cells inside Exosomes and Provides a Blood-Based Diagnostic for ALT Activity.
Article in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 25 citations in OpenAlex.
- Telomere-driven dysfunctional changes in gynecological cancers: mechanistic insights, biomarker potential, and therapeutic targeting.Frontiers in cell and developmental biology · 2026Review
- Anellovirus protein encoded byProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Review
- Distinct mechanisms underlying extrachromosomal telomere DNA generation in ALT cancers.Nucleic acids research · 2025Article
- Cellular adaptations impact the biological activity of naphthalene diimide G-quadruplex ligands in ALT-positive osteosarcoma cells.Cell death & disease · 2025Article
- Telomere Maintenance and DNA Repair: A Bidirectional Relationship in Cancer Biology and Therapy.Cancers · 2025Review
- Exceptional response to the ATR inhibitor, camonsertib, in a patient with ALT+ metastatic melanoma.NPJ precision oncology · 2025Article
- Detection of Alternative Lengthening of Telomeres via Chromogenic In Situ Hybridization for the Prognostication of PanNETs and Other Neoplasms.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2025Article
- Locking the gates of immortality: targeting alternative lengthening of telomeres (ALT) pathways.Medical oncology (Northwood, London, England) · 2025Review
- Beginning at the ends: telomere and telomere-based cancer therapeutics.Molecular genetics and genomics : MGG · 2024Review
- A First-in-Class High-Throughput Screen to Discover Modulators of the Alternative Lengthening of Telomeres (ALT) Pathway.ACS pharmacology & translational science · 2024Article
- Vitronectin Levels in the Plasma of Neuroblastoma Patients and Culture Media of 3D Models: A Prognostic Circulating Biomarker?International journal of molecular sciences · 2024Article
- Alternative lengthening of telomeres: mechanism and the pathogenesis of cancer.Journal of clinical pathology · 2024Article
- Prevalence of alternative lengthening of telomeres in pediatric sarcomas determined by the telomeric DNA C-circle assay.Frontiers in oncology · 2024Article
- Telomeres and telomerase in Sarcoma disease and therapy.International journal of medical sciences · 2024Review
- Article
- Reprint of: The Diagnostic and Prognostic Utility of Incorporating DAXX, ATRX, and Alternative Lengthening of Telomeres (ALT) to the Evaluation of Pancreatic Neuroendocrine Tumors (PanNETs).Human pathology · 2023Review
- Telomere maintenance in African trypanosomes.Frontiers in molecular biosciences · 2023Review
- The diagnostic and prognostic utility of incorporating DAXX, ATRX, and alternative lengthening of telomeres to the evaluation of pancreatic neuroendocrine tumors.Human pathology · 2022Review
- Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
C-Circles, self-primed telomeric C-strand templates for rolling circle amplification, are the only known alternative-lengthening-of-telomeres (ALT)-specific molecule. However, little is known about the biology of C-Circles and if they may be clinically useful. Here we show that C-Circles are secreted by ALT+ cancer cells inside exosomes, and that a blood-based C-Circle Assay (CCA) can provide an accurate diagnostic for ALT activity. Extracellular vesicles were isolated by differential centrifugation from the growth media of lung adenocarcinoma, glioblastoma, neuroblastoma, osteosarcoma, and soft tissue sarcoma cell lines, and C-Circles were detected in the exosome fraction from all eleven ALT+ cancer cell lines and not in any extracellular fraction from the eight matching telomerase positive cancer cell lines or the normal fibroblast strain. The existence of C-Circles in ALT+ exosomes was confirmed with exosomes isolated by iodixanol gradient separation and CD81-immunoprecipitation, and C-Circles in the exosomes were protected from nucleases. On average, 0.4% of the total ALT+ intracellular C-Circles were secreted in the exosomes every 24 h. Comparing the serum-based and tumor-based CCAs in 35 high risk neuroblastoma patients divided randomly into ALT+ threshold derivation and validation groups, we found the serum-based CCA to have 100% sensitivity (6/6), 70% specificity (7/10), and 81% concordance (13/16). We conclude that the secretion of C-Circles by ALT+ cancer cells in the exosomes provides a stable blood-based biomarker and a potential clinical diagnostic for ALT activity.
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