دورية أكاديمية
Genomic hallmarks and therapeutic implications of G0 cell cycle arrest in cancer
| العنوان: | Genomic hallmarks and therapeutic implications of G0 cell cycle arrest in cancer |
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| المؤلفون: | Wiecek, AJ, Cutty, SJ, Kornai, D, Parreno-Centeno, M, Gourmet, LE, Tagliazucchi, GM, Jacobson, DH, Zhang, P, Xiong, L, Bond, GL, Barr, AR, Secrier, M |
| بيانات النشر: | BMC |
| سنة النشر: | 2023 |
| المجموعة: | Imperial College London: Spiral |
| جغرافية الموضوع: | England |
| الوصف: | BACKGROUND: Therapy resistance in cancer is often driven by a subpopulation of cells that are temporarily arrested in a non-proliferative G0 state, which is difficult to capture and whose mutational drivers remain largely unknown. RESULTS: We develop methodology to robustly identify this state from transcriptomic signals and characterise its prevalence and genomic constraints in solid primary tumours. We show that G0 arrest preferentially emerges in the context of more stable, less mutated genomes which maintain TP53 integrity and lack the hallmarks of DNA damage repair deficiency, while presenting increased APOBEC mutagenesis. We employ machine learning to uncover novel genomic dependencies of this process and validate the role of the centrosomal gene CEP89 as a modulator of proliferation and G0 arrest capacity. Lastly, we demonstrate that G0 arrest underlies unfavourable responses to various therapies exploiting cell cycle, kinase signalling and epigenetic mechanisms in single-cell data. CONCLUSIONS: We propose a G0 arrest transcriptional signature that is linked with therapeutic resistance and can be used to further study and clinically track this state. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1474-7596 |
| العلاقة: | Genome Biology; http://hdl.handle.net/10044/1/104713Test |
| DOI: | 10.1186/s13059-023-02963-4 |
| الإتاحة: | https://doi.org/10.1186/s13059-023-02963-4Test http://hdl.handle.net/10044/1/104713Test |
| حقوق: | © The Author(s) 2023. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0Test/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0Test/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. ; http://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.8CC7A9E2 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 14747596 |
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| DOI: | 10.1186/s13059-023-02963-4 |