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Comprehensive characterization of 536 patient-derived xenograft models prioritizes candidates for targeted treatment

Development of candidate cancer treatments is a resource-intensive process, with the research community continuing to investigate options beyond static genomic characterization. Toward this goal, we have established the genomic landscapes of 536 patient-derived xenograft (PDX) models across 25 cance...

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Autores principales: Sun, Hua, Cao, Song, Mashl, R. Jay, Mo, Chia-Kuei, Zaccaria, Simone, Wendl, Michael C., Davies, Sherri R., Bailey, Matthew H., Primeau, Tina M., Hoog, Jeremy, Mudd, Jacqueline L., Dean, Dennis A., Patidar, Rajesh, Chen, Li, Wyczalkowski, Matthew A., Jayasinghe, Reyka G., Rodrigues, Fernanda Martins, Terekhanova, Nadezhda V., Li, Yize, Lim, Kian-Huat, Wang-Gillam, Andrea, Van Tine, Brian A., Ma, Cynthia X., Aft, Rebecca, Fuh, Katherine C., Schwarz, Julie K., Zevallos, Jose P., Puram, Sidharth V., Dipersio, John F., Davis-Dusenbery, Brandi, Ellis, Matthew J., Lewis, Michael T., Davies, Michael A., Herlyn, Meenhard, Fang, Bingliang, Roth, Jack A., Welm, Alana L., Welm, Bryan E., Meric-Bernstam, Funda, Chen, Feng, Fields, Ryan C., Li, Shunqiang, Govindan, Ramaswamy, Doroshow, James H., Moscow, Jeffrey A., Evrard, Yvonne A., Chuang, Jeffrey H., Raphael, Benjamin J., Ding, Li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8384880/
https://www.ncbi.nlm.nih.gov/pubmed/34429404
http://dx.doi.org/10.1038/s41467-021-25177-3
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author Sun, Hua
Cao, Song
Mashl, R. Jay
Mo, Chia-Kuei
Zaccaria, Simone
Wendl, Michael C.
Davies, Sherri R.
Bailey, Matthew H.
Primeau, Tina M.
Hoog, Jeremy
Mudd, Jacqueline L.
Dean, Dennis A.
Patidar, Rajesh
Chen, Li
Wyczalkowski, Matthew A.
Jayasinghe, Reyka G.
Rodrigues, Fernanda Martins
Terekhanova, Nadezhda V.
Li, Yize
Lim, Kian-Huat
Wang-Gillam, Andrea
Van Tine, Brian A.
Ma, Cynthia X.
Aft, Rebecca
Fuh, Katherine C.
Schwarz, Julie K.
Zevallos, Jose P.
Puram, Sidharth V.
Dipersio, John F.
Davis-Dusenbery, Brandi
Ellis, Matthew J.
Lewis, Michael T.
Davies, Michael A.
Herlyn, Meenhard
Fang, Bingliang
Roth, Jack A.
Welm, Alana L.
Welm, Bryan E.
Meric-Bernstam, Funda
Chen, Feng
Fields, Ryan C.
Li, Shunqiang
Govindan, Ramaswamy
Doroshow, James H.
Moscow, Jeffrey A.
Evrard, Yvonne A.
Chuang, Jeffrey H.
Raphael, Benjamin J.
Ding, Li
author_facet Sun, Hua
Cao, Song
Mashl, R. Jay
Mo, Chia-Kuei
Zaccaria, Simone
Wendl, Michael C.
Davies, Sherri R.
Bailey, Matthew H.
Primeau, Tina M.
Hoog, Jeremy
Mudd, Jacqueline L.
Dean, Dennis A.
Patidar, Rajesh
Chen, Li
Wyczalkowski, Matthew A.
Jayasinghe, Reyka G.
Rodrigues, Fernanda Martins
Terekhanova, Nadezhda V.
Li, Yize
Lim, Kian-Huat
Wang-Gillam, Andrea
Van Tine, Brian A.
Ma, Cynthia X.
Aft, Rebecca
Fuh, Katherine C.
Schwarz, Julie K.
Zevallos, Jose P.
Puram, Sidharth V.
Dipersio, John F.
Davis-Dusenbery, Brandi
Ellis, Matthew J.
Lewis, Michael T.
Davies, Michael A.
Herlyn, Meenhard
Fang, Bingliang
Roth, Jack A.
Welm, Alana L.
Welm, Bryan E.
Meric-Bernstam, Funda
Chen, Feng
Fields, Ryan C.
Li, Shunqiang
Govindan, Ramaswamy
Doroshow, James H.
Moscow, Jeffrey A.
Evrard, Yvonne A.
Chuang, Jeffrey H.
Raphael, Benjamin J.
Ding, Li
author_sort Sun, Hua
collection PubMed
description Development of candidate cancer treatments is a resource-intensive process, with the research community continuing to investigate options beyond static genomic characterization. Toward this goal, we have established the genomic landscapes of 536 patient-derived xenograft (PDX) models across 25 cancer types, together with mutation, copy number, fusion, transcriptomic profiles, and NCI-MATCH arms. Compared with human tumors, PDXs typically have higher purity and fit to investigate dynamic driver events and molecular properties via multiple time points from same case PDXs. Here, we report on dynamic genomic landscapes and pharmacogenomic associations, including associations between activating oncogenic events and drugs, correlations between whole-genome duplications and subclone events, and the potential PDX models for NCI-MATCH trials. Lastly, we provide a web portal having comprehensive pan-cancer PDX genomic profiles and source code to facilitate identification of more druggable events and further insights into PDXs’ recapitulation of human tumors.
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spelling pubmed-83848802021-10-04 Comprehensive characterization of 536 patient-derived xenograft models prioritizes candidates for targeted treatment Sun, Hua Cao, Song Mashl, R. Jay Mo, Chia-Kuei Zaccaria, Simone Wendl, Michael C. Davies, Sherri R. Bailey, Matthew H. Primeau, Tina M. Hoog, Jeremy Mudd, Jacqueline L. Dean, Dennis A. Patidar, Rajesh Chen, Li Wyczalkowski, Matthew A. Jayasinghe, Reyka G. Rodrigues, Fernanda Martins Terekhanova, Nadezhda V. Li, Yize Lim, Kian-Huat Wang-Gillam, Andrea Van Tine, Brian A. Ma, Cynthia X. Aft, Rebecca Fuh, Katherine C. Schwarz, Julie K. Zevallos, Jose P. Puram, Sidharth V. Dipersio, John F. Davis-Dusenbery, Brandi Ellis, Matthew J. Lewis, Michael T. Davies, Michael A. Herlyn, Meenhard Fang, Bingliang Roth, Jack A. Welm, Alana L. Welm, Bryan E. Meric-Bernstam, Funda Chen, Feng Fields, Ryan C. Li, Shunqiang Govindan, Ramaswamy Doroshow, James H. Moscow, Jeffrey A. Evrard, Yvonne A. Chuang, Jeffrey H. Raphael, Benjamin J. Ding, Li Nat Commun Article Development of candidate cancer treatments is a resource-intensive process, with the research community continuing to investigate options beyond static genomic characterization. Toward this goal, we have established the genomic landscapes of 536 patient-derived xenograft (PDX) models across 25 cancer types, together with mutation, copy number, fusion, transcriptomic profiles, and NCI-MATCH arms. Compared with human tumors, PDXs typically have higher purity and fit to investigate dynamic driver events and molecular properties via multiple time points from same case PDXs. Here, we report on dynamic genomic landscapes and pharmacogenomic associations, including associations between activating oncogenic events and drugs, correlations between whole-genome duplications and subclone events, and the potential PDX models for NCI-MATCH trials. Lastly, we provide a web portal having comprehensive pan-cancer PDX genomic profiles and source code to facilitate identification of more druggable events and further insights into PDXs’ recapitulation of human tumors. Nature Publishing Group UK 2021-08-24 /pmc/articles/PMC8384880/ /pubmed/34429404 http://dx.doi.org/10.1038/s41467-021-25177-3 Text en © The Author(s) 2021, corrected publication 2021 https://creativecommons.org/licenses/by/4.0/Open Access 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Sun, Hua
Cao, Song
Mashl, R. Jay
Mo, Chia-Kuei
Zaccaria, Simone
Wendl, Michael C.
Davies, Sherri R.
Bailey, Matthew H.
Primeau, Tina M.
Hoog, Jeremy
Mudd, Jacqueline L.
Dean, Dennis A.
Patidar, Rajesh
Chen, Li
Wyczalkowski, Matthew A.
Jayasinghe, Reyka G.
Rodrigues, Fernanda Martins
Terekhanova, Nadezhda V.
Li, Yize
Lim, Kian-Huat
Wang-Gillam, Andrea
Van Tine, Brian A.
Ma, Cynthia X.
Aft, Rebecca
Fuh, Katherine C.
Schwarz, Julie K.
Zevallos, Jose P.
Puram, Sidharth V.
Dipersio, John F.
Davis-Dusenbery, Brandi
Ellis, Matthew J.
Lewis, Michael T.
Davies, Michael A.
Herlyn, Meenhard
Fang, Bingliang
Roth, Jack A.
Welm, Alana L.
Welm, Bryan E.
Meric-Bernstam, Funda
Chen, Feng
Fields, Ryan C.
Li, Shunqiang
Govindan, Ramaswamy
Doroshow, James H.
Moscow, Jeffrey A.
Evrard, Yvonne A.
Chuang, Jeffrey H.
Raphael, Benjamin J.
Ding, Li
Comprehensive characterization of 536 patient-derived xenograft models prioritizes candidates for targeted treatment
title Comprehensive characterization of 536 patient-derived xenograft models prioritizes candidates for targeted treatment
title_full Comprehensive characterization of 536 patient-derived xenograft models prioritizes candidates for targeted treatment
title_fullStr Comprehensive characterization of 536 patient-derived xenograft models prioritizes candidates for targeted treatment
title_full_unstemmed Comprehensive characterization of 536 patient-derived xenograft models prioritizes candidates for targeted treatment
title_short Comprehensive characterization of 536 patient-derived xenograft models prioritizes candidates for targeted treatment
title_sort comprehensive characterization of 536 patient-derived xenograft models prioritizes candidates for targeted treatment
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8384880/
https://www.ncbi.nlm.nih.gov/pubmed/34429404
http://dx.doi.org/10.1038/s41467-021-25177-3
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