Document Type
Article
Publication Date
8-24-2021
Publication Title
Nat Commun
Keywords
Animals, Disease Models, Animal, Female, Gene Expression Regulation, Neoplastic, Genome, Genomics, Heterografts, Humans, Male, Mice, Models, Biological, Mutation, Neoplasms, Transcriptome, Xenograft Model Antitumor Assays
JAX Location
JGM, JMG
JAX Source
Nat Commun 2021 Aug 24; 12(1):5086
Volume
12
Issue
1
First Page
5086
Last Page
5086
ISSN
2041-1723
PMID
34429404
DOI
https://doi.org/10.1038/s41467-021-25177-3
Grant
CA034196
Abstract
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.
Recommended Citation
Sun H,
Cao S,
Mashl R,
Mo C,
Zaccaria S,
Wendl M,
Davies S,
Bailey M,
Primeau T,
Hoog J,
Mudd J,
Dean D,
Patidar R,
Chen L,
Wyczalkowski M,
Jayasinghe R,
Rodrigues F,
Terekhanova N,
Li Y,
Lim K,
Wang-Gillam A,
Van Tine B,
Ma C,
Aft R,
Fuh K,
Schwarz J,
Zevallos J,
Puram S,
Dipersio J,
Consortium NP,
Davis-Dusenbery B,
Ellis M,
Lewis M,
Davies M,
Herlyn M,
Fang B,
Roth J,
Welm A,
Welm B,
Meric-Bernstam F,
Chen F,
Fields R,
Li S,
Govindan R,
Doroshow J,
Moscow J,
Evrard Y,
Chuang J,
Raphael B,
Ding L,
Bult C,
Robinson P.
Comprehensive characterization of 536 patient-derived xenograft models prioritizes candidatesfor targeted treatment. Nat Commun 2021 Aug 24; 12(1):5086
Comments
The Jackson Laboratory (JAX) PDX resource data were supported by the National Cancer Institute under the JAX Cancer Center NCI Grant (Award Number P30CA034196). The genomic data for JAX PDX tumors used in this work were generated by JAX Genome Technologies and Single Cell Biology Scientific Service.
Carol Bult and Peter Robinson are members of the NCI PDXNet Consortium.
This article is licensed under a Creative Commons Attribution 4.0 International License.