Identification of full-length circular RNAs linked with therapy resistance of pediatric cancers
Abstract Resistance to cancer treatment remains the leading cause of cancer-related deaths. In tumors with low mutational burden such as pediatric cancers, alternative transcripts, including circular RNAs (circRNAs), have been identified as involved in treatment resistance. However, their isoforms are often missed by commonly used short-read sequencing. Here, we employ long-read sequencing to identify full-length circRNA isoforms associated with resistance in ALK -driven pediatric cancers. Using cell models and a cohort of ALK -translocated anaplastic large-cell lymphoma (ALK+ ALCL) patients, two circRNAs were detected as specifically upregulated in resistant cases and associated with worse disease outcomes. Similar findings were observed in the pediatric cancer neuroblastoma. These circRNAs were also more abundant in liquid biopsies from ALKi-resistant ALK+ ALCL and neuroblastoma patients. This demonstrates that long-read sequencing allows for uncovering disease-relevant circRNA isoforms that could serve as biomarkers for resistance detection in a clinical setting.
Authors
- Christine Gaspin (ORCID: https://orcid.org/0000-0003-0304-5186)
- Annabell Szymansky (ORCID: https://orcid.org/0000-0003-4797-4526)
- Laurence Lamant (ORCID: https://orcid.org/0000-0002-1123-7658)
- Fabienne Meggetto (ORCID: https://orcid.org/0000-0002-2610-0144)
- Steffen Fuchs (ORCID: https://orcid.org/0000-0001-9619-4329)
- Hedwig E. Deubzer
- Véronique Vergé (ORCID: https://orcid.org/0000-0002-3233-5978)
- Cyril Quivoron (ORCID: https://orcid.org/0000-0002-9871-0187)
- Marco Lodrini
- Stéphane Pyronnet (ORCID: https://orcid.org/0000-0002-9562-5112)
- Angelika Eggert (ORCID: https://orcid.org/0000-0003-3476-8184)
- Chloé Bessière (ORCID: https://orcid.org/0000-0001-7518-3559)
- Elissa Andraos (ORCID: https://orcid.org/0000-0003-0630-3742)
- Charlotte Rigaud (ORCID: https://orcid.org/0000-0002-9787-0314)
- Loélia Babin (ORCID: https://orcid.org/0000-0002-0188-6582)
- Johannes Markus Riepl
Institutions
- Centre National de la Recherche Scientifique (FR)
- Helmholtz Association of German Research Centres (DE)
- Université Toulouse III - Paul Sabatier (FR)
- Inserm (FR)
- Max Delbrück Center (DE)
- Université Paris-Saclay (FR)
- Institut Gustave Roussy (FR)
- Humboldt-Universität zu Berlin (DE)
- Centre de Recherches en Cancérologie de Toulouse (FR)
- Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (FR)
- German Cancer Society (DE)
- Essen University Hospital (DE)
- German Centre for Cardiovascular Research (DE)
- Berlin Institute of Health at Charité - Universitätsmedizin Berlin (DE)
- Génétique Physiologie et Systèmes d'Elevage (FR)
- University of Duisburg-Essen (DE)
Publication Details
- Journal
- medRxiv
- Published
- 2025-12-04
- DOI
- https://doi.org/10.64898/2025.11.28.25340833
- Primary Topic
- Circular RNAs in diseases
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- L'Oreal USA
- Institut National de la Santé et de la Recherche Médicale
- Fondation ARC pour la Recherche sur le Cancer
- Fondation de France
- Région Occitanie Pyrénées-Méditerranée
- Fondation Toulouse Cancer Santé