Pan-cancer whole-genome analyses of metastatic solid tumours
| العنوان: | Pan-cancer whole-genome analyses of metastatic solid tumours |
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| المؤلفون: | Arne Van Hoeck, Peter Priestley, Egbert F. Smit, Wendy Onstenk, Edwin Cuppen, Korneel Duyvesteyn, Ewart de Bruijn, Haiko J. Bloemendal, Jonathan Baber, Paul Roepman, Charles Shale, Carla M.L. van Herpen, Susan Haidari, Vivianne C. G. Tjan-Heijnen, Emile E. Voest, Martijn P. Lolkema, Mircea Voda, Stefan Sleijfer, Petronella O. Witteveen, Mariette Labots, Neeltje Steeghs |
| المساهمون: | Medical Oncology, Medical oncology, CCA - Cancer biology and immunology, CCA - Imaging and biomarkers, CCA - Cancer Treatment and quality of life, Pulmonary medicine, Interne Geneeskunde, MUMC+: MA Medische Oncologie (9), RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy |
| المصدر: | Nature Priestley, P, Baber, J, Lolkema, M P, Steeghs, N, de Bruijn, E, Shale, C, Duyvesteyn, K, Haidari, S, van Hoeck, A, Onstenk, W, Roepman, P, Voda, M, Bloemendal, H J, Tjan-Heijnen, V C G, van Herpen, C M L, Labots, M, Witteveen, P O, Smit, E F, Sleijfer, S, Voest, E E & Cuppen, E 2019, ' Pan-cancer whole-genome analyses of metastatic solid tumours ', Nature, vol. 575, no. 7781, pp. 210-216 . https://doi.org/10.1038/s41586-019-1689-yTest Nature, 575(7781), 210. Nature Publishing Group Nature, 575, 210-216 Nature, 575(7781), 210-216. Nature Publishing Group Nature, 575, 7781, pp. 210-216 |
| بيانات النشر: | Nature Publishing Group UK, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Oncology, Male, SELECTION, VARIANTS, Genome, Germline, 0302 clinical medicine, INDEL Mutation, Neoplasms, Gene duplication, Cancer genomics, HETEROGENEITY, Neoplasm Metastasis, Precision Medicine, Non-U.S. Gov't, Cause of death, 0303 health sciences, Multidisciplinary, Research Support, Non-U.S. Gov't, 3. Good health, 030220 oncology & carcinogenesis, Female, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9], medicine.medical_specialty, DNA Copy Number Variations, GENETICS, Research Support, Article, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Internal medicine, GERMLINE, medicine, Journal Article, Humans, General, Gene, 030304 developmental biology, Whole genome sequencing, Whole Genome Sequencing, LANDSCAPE, business.industry, Information Dissemination, MUTATIONS, Precision medicine, EVOLUTION, Clone Cells, Clinical trial, Mutation, PATTERNS, UPDATE, business |
| الوصف: | Metastatic cancer is a major cause of death and is associated with poor treatment efficacy. A better understanding of the characteristics of late-stage cancer is required to help adapt personalized treatments, reduce overtreatment and improve outcomes. Here we describe the largest, to our knowledge, pan-cancer study of metastatic solid tumour genomes, including whole-genome sequencing data for 2,520 pairs of tumour and normal tissue, analysed at median depths of 106× and 38×, respectively, and surveying more than 70 million somatic variants. The characteristic mutations of metastatic lesions varied widely, with mutations that reflect those of the primary tumour types, and with high rates of whole-genome duplication events (56%). Individual metastatic lesions were relatively homogeneous, with the vast majority (96%) of driver mutations being clonal and up to 80% of tumour-suppressor genes being inactivated bi-allelically by different mutational mechanisms. Although metastatic tumour genomes showed similar mutational landscape and driver genes to primary tumours, we find characteristics that could contribute to responsiveness to therapy or resistance in individual patients. We implement an approach for the review of clinically relevant associations and their potential for actionability. For 62% of patients, we identify genetic variants that may be used to stratify patients towards therapies that either have been approved or are in clinical trials. This demonstrates the importance of comprehensive genomic tumour profiling for precision medicine in cancer. The mutational landscape of metastatic cancer genomes is analysed in a large-scale, pan-cancer study of metastatic solid tumours that includes whole-genome sequencing of 2,520 tumour–normal tissue pairs. |
| وصف الملف: | image/pdf; application/pdf |
| اللغة: | English |
| تدمد: | 1476-4687 0028-0836 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::151dfcf6ddc15faa4370dbff734c9c5fTest http://europepmc.org/articles/PMC6872491Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....151dfcf6ddc15faa4370dbff734c9c5f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14764687 00280836 |
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