دورية أكاديمية
Copy number architectures define treatment-mediated selection of lethal prostate cancer clones
| العنوان: | Copy number architectures define treatment-mediated selection of lethal prostate cancer clones |
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| المؤلفون: | Hasan, A. M. Mahedi, Cremaschi, Paolo, Wetterskog, Daniel, Jayaram, Anuradha, Wong, Stephen Q., Williams, Scott, Pasam, Anupama, Trigos, Anna, Trujillo, Blanca, Grist, Emily, Friedrich, Stefanie, Vainauskas, Osvaldas, Parry, Marina, Ismail, Mazlina, Devlies, Wout, Wingate, Anna, Linch, Mark, Naceur-Lombardelli, Cristina, Zaccaria, Simone, Hessey, Sonya, Shiu, Kai-Keen, Bridgewater, John, Hochhauser, Daniel, Forster, Martin, Lee, Siow-Ming, Ahmad, Tanya, Papadatos-Pastos, Dionysis, Janes, Sam, Van Loo, Peter, Enfield, Katey, McGranahan, Nicholas, Huebner, Ariana, Quezada, Sergio, Beck, Stephan, Parker, Peter, Enver, Tariq, Hynds, Robert E., Pearce, David R., Falzon, Mary, Proctor, Ian, Sinclair, Ron, Lok, Chi-wah, Rhodes, Zoe, Moore, David, Marafioti, Teresa, Mitchison, Miriam, Ellery, Peter, Sivakumar, Monica, Brandner, Sebastian |
| المساهمون: | Cancer Research UK |
| المصدر: | Nature Communications ; volume 14, issue 1 ; ISSN 2041-1723 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary |
| الوصف: | Despite initial responses to hormone treatment, metastatic prostate cancer invariably evolves to a lethal state. To characterize the intra-patient evolutionary relationships of metastases that evade treatment, we perform genome-wide copy number profiling and bespoke approaches targeting the androgen receptor (AR) on 167 metastatic regions from 11 organs harvested post-mortem from 10 men who died from prostate cancer. We identify diverse and patient-unique alterations clustering around the AR in metastases from every patient with evidence of independent acquisition of related genomic changes within an individual and, in some patients, the co-existence of AR -neutral clones. Using the genomic boundaries of pan-autosome copy number changes, we confirm a common clone of origin across metastases and diagnostic biopsies, and identified in individual patients, clusters of metastases occupied by dominant clones with diverged autosomal copy number alterations. These autosome-defined clusters are characterized by cluster-specific AR gene architectures, and in two index cases are topologically more congruent than by chance ( p -values 3.07 × 10 −8 and 6.4 × 10 −4 ). Integration with anatomical sites suggests patterns of spread and points of genomic divergence. Here, we show that copy number boundaries identify treatment-selected clones with putatively distinct lethal trajectories. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/s41467-023-40315-9 |
| الإتاحة: | https://doi.org/10.1038/s41467-023-40315-9Test https://www.nature.com/articles/s41467-023-40315-9.pdfTest https://www.nature.com/articles/s41467-023-40315-9Test |
| حقوق: | https://creativecommons.org/licenses/by/4.0Test ; https://creativecommons.org/licenses/by/4.0Test |
| رقم الانضمام: | edsbas.FAC82138 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41467-023-40315-9 |
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