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A Genomically and Clinically Annotated Patient Derived Xenograft (PDX) Resource for Preclinical Research in Non-Small Cell Lung Cancer

Xing Yi Woo, Anuj Srivastava, Philip C. Mack, Joel H. Graber, Brian J. Sanderson, View ORCID ProfileMichael W. Lloyd, Mandy Chen, Sergii Domanskyi, Regina Gandour-Edwards, Rebekah A. Tsai, James Keck, Mingshan Cheng, Margaret Bundy, Emily L. Jocoy, Jonathan W. Riess, William Holland, Stephen C. Grubb, James G. Peterson, Grace A. Stafford, Carolyn Paisie, Steven B. Neuhauser, R. Krishna Murthy Karuturi, Joshy George, Allen K. Simons, Margaret Chavaree, Clifford G. Tepper, Neal Goodwin, Susan D. Airhart, Primo N. Lara Jr., Thomas H. Openshaw, Edison T. Liu, David R. Gandara, View ORCID ProfileCarol J. Bult
doi: https://doi.org/10.1101/2022.03.06.483171
Xing Yi Woo
4The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut, USA
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Anuj Srivastava
4The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut, USA
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Philip C. Mack
1University of California Davis Comprehensive Cancer Center, Sacramento, California, USA
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Joel H. Graber
2The Jackson Laboratory for Mammalian Genetics, Bar Harbor, Maine, USA
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Brian J. Sanderson
4The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut, USA
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Michael W. Lloyd
2The Jackson Laboratory for Mammalian Genetics, Bar Harbor, Maine, USA
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Mandy Chen
2The Jackson Laboratory for Mammalian Genetics, Bar Harbor, Maine, USA
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Sergii Domanskyi
2The Jackson Laboratory for Mammalian Genetics, Bar Harbor, Maine, USA
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Regina Gandour-Edwards
1University of California Davis Comprehensive Cancer Center, Sacramento, California, USA
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Rebekah A. Tsai
1University of California Davis Comprehensive Cancer Center, Sacramento, California, USA
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James Keck
3The Jackson Laboratory, Sacramento, California, USA
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Mingshan Cheng
3The Jackson Laboratory, Sacramento, California, USA
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Margaret Bundy
3The Jackson Laboratory, Sacramento, California, USA
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Emily L. Jocoy
3The Jackson Laboratory, Sacramento, California, USA
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Jonathan W. Riess
1University of California Davis Comprehensive Cancer Center, Sacramento, California, USA
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William Holland
1University of California Davis Comprehensive Cancer Center, Sacramento, California, USA
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Stephen C. Grubb
2The Jackson Laboratory for Mammalian Genetics, Bar Harbor, Maine, USA
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James G. Peterson
2The Jackson Laboratory for Mammalian Genetics, Bar Harbor, Maine, USA
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Grace A. Stafford
2The Jackson Laboratory for Mammalian Genetics, Bar Harbor, Maine, USA
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Carolyn Paisie
4The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut, USA
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Steven B. Neuhauser
2The Jackson Laboratory for Mammalian Genetics, Bar Harbor, Maine, USA
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R. Krishna Murthy Karuturi
4The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut, USA
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Joshy George
4The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut, USA
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Allen K. Simons
2The Jackson Laboratory for Mammalian Genetics, Bar Harbor, Maine, USA
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Margaret Chavaree
2The Jackson Laboratory for Mammalian Genetics, Bar Harbor, Maine, USA
5Eastern Maine Medical Center, Lafayette Family Cancer Center, Brewer, Maine, USA
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Clifford G. Tepper
1University of California Davis Comprehensive Cancer Center, Sacramento, California, USA
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Neal Goodwin
3The Jackson Laboratory, Sacramento, California, USA
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Susan D. Airhart
2The Jackson Laboratory for Mammalian Genetics, Bar Harbor, Maine, USA
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Primo N. Lara Jr.
1University of California Davis Comprehensive Cancer Center, Sacramento, California, USA
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Thomas H. Openshaw
5Eastern Maine Medical Center, Lafayette Family Cancer Center, Brewer, Maine, USA
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Edison T. Liu
2The Jackson Laboratory for Mammalian Genetics, Bar Harbor, Maine, USA
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David R. Gandara
1University of California Davis Comprehensive Cancer Center, Sacramento, California, USA
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Carol J. Bult
2The Jackson Laboratory for Mammalian Genetics, Bar Harbor, Maine, USA
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  • ORCID record for Carol J. Bult
  • For correspondence: Carol.Bult@jax.org
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Abstract

Patient-derived xenograft models (PDXs) are an effective preclinical in vivo platform for testing the efficacy of novel drug and drug combinations for cancer therapeutics. Here we describe a repository of 79 genomically and clinically annotated lung cancer PDXs available from The Jackson Laboratory that have been extensively characterized for histopathological features, mutational profiles, gene expression, and copy number aberrations. Most of the PDXs are models of non-small cell lung cancer (NSCLC), including 37 lung adenocarcinoma (LUAD) and 33 lung squamous cell carcinoma (LUSC) models. Other lung cancer models in the repository include four small cell carcinomas, two large cell neuroendocrine carcinomas, two adenosquamous carcinomas, and one pleomorphic carcinoma. Models with both de novo and acquired resistance to targeted therapies with tyrosine kinase inhibitors are available in the collection. The genomic profiles of the LUAD and LUSC PDX models are consistent with those observed in patient tumors of the same tumor type from The Cancer Genome Atlas (TCGA) and to previously characterized gene expression-based molecular subtypes. Clinically relevant mutations identified in the original patient tumors were confirmed in engrafted tumors. Treatment studies performed for a subset of the models recapitulated the responses expected based on the observed genomic profiles.

Significance The collection of lung cancer Patient Derived Xenograft (PDX) models maintained at The Jackson Laboratory retain both the histologic features and treatment-relevant genomic alterations observed in the originating patient tumors and show expected responses to treatment with standard-of-care agents. The models serve as a valuable preclinical platform for translational cancer research. Information and data for the models are freely available from the Mouse Models of Human Cancer database (MMHCdb, http://tumor.informatics.jax.org/mtbwi/pdxSearch.do).

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • http://tumor.informatics.jax.org/mtbwi/pdxSearch.do

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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A Genomically and Clinically Annotated Patient Derived Xenograft (PDX) Resource for Preclinical Research in Non-Small Cell Lung Cancer
Xing Yi Woo, Anuj Srivastava, Philip C. Mack, Joel H. Graber, Brian J. Sanderson, Michael W. Lloyd, Mandy Chen, Sergii Domanskyi, Regina Gandour-Edwards, Rebekah A. Tsai, James Keck, Mingshan Cheng, Margaret Bundy, Emily L. Jocoy, Jonathan W. Riess, William Holland, Stephen C. Grubb, James G. Peterson, Grace A. Stafford, Carolyn Paisie, Steven B. Neuhauser, R. Krishna Murthy Karuturi, Joshy George, Allen K. Simons, Margaret Chavaree, Clifford G. Tepper, Neal Goodwin, Susan D. Airhart, Primo N. Lara Jr., Thomas H. Openshaw, Edison T. Liu, David R. Gandara, Carol J. Bult
bioRxiv 2022.03.06.483171; doi: https://doi.org/10.1101/2022.03.06.483171
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A Genomically and Clinically Annotated Patient Derived Xenograft (PDX) Resource for Preclinical Research in Non-Small Cell Lung Cancer
Xing Yi Woo, Anuj Srivastava, Philip C. Mack, Joel H. Graber, Brian J. Sanderson, Michael W. Lloyd, Mandy Chen, Sergii Domanskyi, Regina Gandour-Edwards, Rebekah A. Tsai, James Keck, Mingshan Cheng, Margaret Bundy, Emily L. Jocoy, Jonathan W. Riess, William Holland, Stephen C. Grubb, James G. Peterson, Grace A. Stafford, Carolyn Paisie, Steven B. Neuhauser, R. Krishna Murthy Karuturi, Joshy George, Allen K. Simons, Margaret Chavaree, Clifford G. Tepper, Neal Goodwin, Susan D. Airhart, Primo N. Lara Jr., Thomas H. Openshaw, Edison T. Liu, David R. Gandara, Carol J. Bult
bioRxiv 2022.03.06.483171; doi: https://doi.org/10.1101/2022.03.06.483171

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