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Genomic heterogeneity as a barrier to precision oncology in urothelial cancer

Precision oncology relies on the accurate molecular characterization of individual patients with cancer at the time of treatment initiation. However, tumor molecular profiles are not static, and cancers continually evolve because of ongoing mutagenesis and clonal selection. Here, we performed genomi...

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Autores principales: Clinton, Timothy N., Chen, Ziyu, Wise, Hannah, Lenis, Andrew T., Chavan, Shweta, Donoghue, Mark T.A., Almassi, Nima, Chu, Carissa E., Dason, Shawn, Rao, Pavitra, Rodrigues, James A., Vasani, Naresh B., Ridouani, Fourat, Rosenberg, Jonathan E., Bajorin, Dean F., Teo, Min Yuen, Bochner, Bernard H., Berger, Michael F., Ostrovnaya, Irina, Pietzak, Eugene J., Iyer, Gopa, Gao, Sizhi Paul, Hu, Wenhuo, Al-Ahmadie, Hikmat A., Solit, David B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9882421/
https://www.ncbi.nlm.nih.gov/pubmed/36543146
http://dx.doi.org/10.1016/j.celrep.2022.111859
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author Clinton, Timothy N.
Chen, Ziyu
Wise, Hannah
Lenis, Andrew T.
Chavan, Shweta
Donoghue, Mark T.A.
Almassi, Nima
Chu, Carissa E.
Dason, Shawn
Rao, Pavitra
Rodrigues, James A.
Vasani, Naresh B.
Ridouani, Fourat
Rosenberg, Jonathan E.
Bajorin, Dean F.
Teo, Min Yuen
Bochner, Bernard H.
Berger, Michael F.
Ostrovnaya, Irina
Pietzak, Eugene J.
Iyer, Gopa
Gao, Sizhi Paul
Hu, Wenhuo
Al-Ahmadie, Hikmat A.
Solit, David B.
author_facet Clinton, Timothy N.
Chen, Ziyu
Wise, Hannah
Lenis, Andrew T.
Chavan, Shweta
Donoghue, Mark T.A.
Almassi, Nima
Chu, Carissa E.
Dason, Shawn
Rao, Pavitra
Rodrigues, James A.
Vasani, Naresh B.
Ridouani, Fourat
Rosenberg, Jonathan E.
Bajorin, Dean F.
Teo, Min Yuen
Bochner, Bernard H.
Berger, Michael F.
Ostrovnaya, Irina
Pietzak, Eugene J.
Iyer, Gopa
Gao, Sizhi Paul
Hu, Wenhuo
Al-Ahmadie, Hikmat A.
Solit, David B.
author_sort Clinton, Timothy N.
collection PubMed
description Precision oncology relies on the accurate molecular characterization of individual patients with cancer at the time of treatment initiation. However, tumor molecular profiles are not static, and cancers continually evolve because of ongoing mutagenesis and clonal selection. Here, we performed genomic analyses of primary tumors, metastases, and plasma collected from individual patients to define the concordance of actionable genomic alterations and to identify drivers of metastatic disease progression. We observed a high degree of discordance of actionable genomic alterations, with 23% discordant between primary and metastatic disease sites. Among chromatin-modifying genes, ARID1A mutations, when discordant, were exclusive to the metastatic tumor samples. Our findings indicate that the high degree of lesion-to-lesion genomic heterogeneity may be a barrier to precision oncology approaches for bladder cancer and that circulating tumor DNA profiling may be preferred to tumor sequencing for a subset of patients.
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spelling pubmed-98824212023-01-27 Genomic heterogeneity as a barrier to precision oncology in urothelial cancer Clinton, Timothy N. Chen, Ziyu Wise, Hannah Lenis, Andrew T. Chavan, Shweta Donoghue, Mark T.A. Almassi, Nima Chu, Carissa E. Dason, Shawn Rao, Pavitra Rodrigues, James A. Vasani, Naresh B. Ridouani, Fourat Rosenberg, Jonathan E. Bajorin, Dean F. Teo, Min Yuen Bochner, Bernard H. Berger, Michael F. Ostrovnaya, Irina Pietzak, Eugene J. Iyer, Gopa Gao, Sizhi Paul Hu, Wenhuo Al-Ahmadie, Hikmat A. Solit, David B. Cell Rep Article Precision oncology relies on the accurate molecular characterization of individual patients with cancer at the time of treatment initiation. However, tumor molecular profiles are not static, and cancers continually evolve because of ongoing mutagenesis and clonal selection. Here, we performed genomic analyses of primary tumors, metastases, and plasma collected from individual patients to define the concordance of actionable genomic alterations and to identify drivers of metastatic disease progression. We observed a high degree of discordance of actionable genomic alterations, with 23% discordant between primary and metastatic disease sites. Among chromatin-modifying genes, ARID1A mutations, when discordant, were exclusive to the metastatic tumor samples. Our findings indicate that the high degree of lesion-to-lesion genomic heterogeneity may be a barrier to precision oncology approaches for bladder cancer and that circulating tumor DNA profiling may be preferred to tumor sequencing for a subset of patients. 2022-12-20 /pmc/articles/PMC9882421/ /pubmed/36543146 http://dx.doi.org/10.1016/j.celrep.2022.111859 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ).
spellingShingle Article
Clinton, Timothy N.
Chen, Ziyu
Wise, Hannah
Lenis, Andrew T.
Chavan, Shweta
Donoghue, Mark T.A.
Almassi, Nima
Chu, Carissa E.
Dason, Shawn
Rao, Pavitra
Rodrigues, James A.
Vasani, Naresh B.
Ridouani, Fourat
Rosenberg, Jonathan E.
Bajorin, Dean F.
Teo, Min Yuen
Bochner, Bernard H.
Berger, Michael F.
Ostrovnaya, Irina
Pietzak, Eugene J.
Iyer, Gopa
Gao, Sizhi Paul
Hu, Wenhuo
Al-Ahmadie, Hikmat A.
Solit, David B.
Genomic heterogeneity as a barrier to precision oncology in urothelial cancer
title Genomic heterogeneity as a barrier to precision oncology in urothelial cancer
title_full Genomic heterogeneity as a barrier to precision oncology in urothelial cancer
title_fullStr Genomic heterogeneity as a barrier to precision oncology in urothelial cancer
title_full_unstemmed Genomic heterogeneity as a barrier to precision oncology in urothelial cancer
title_short Genomic heterogeneity as a barrier to precision oncology in urothelial cancer
title_sort genomic heterogeneity as a barrier to precision oncology in urothelial cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9882421/
https://www.ncbi.nlm.nih.gov/pubmed/36543146
http://dx.doi.org/10.1016/j.celrep.2022.111859
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