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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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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. |
format | Online Article Text |
id | pubmed-8384880 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
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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