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Organoid generation from mouse mammary tumors captures the genetic heterogeneity of clinically relevant copy number alterations
Katherine E. Lake, Megan M. Colonetta, Clayton A. Smith, Kenneth Martinez-Algarin, Kaitlyn Saunders, Sakshi Mohta, Jacob Pena, Heather L. McArthur, Sangeetha M. Reddy, Evanthia T. Roussos-Torres, View ORCID ProfileElizabeth H. Chen, View ORCID ProfileIsaac S. Chan
doi: https://doi.org/10.1101/2023.01.29.526141
Katherine E. Lake
1Department of Internal Medicine, Division of Hematology and Oncology, University of Texas Southwestern, Dallas, Texas, USA
2Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA
Megan M. Colonetta
2Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA
3Department of Molecular Biology, University of Texas Southwestern, Dallas, Texas, USA
4Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA
5Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA
Clayton A. Smith
1Department of Internal Medicine, Division of Hematology and Oncology, University of Texas Southwestern, Dallas, Texas, USA
2Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA
Kenneth Martinez-Algarin
1Department of Internal Medicine, Division of Hematology and Oncology, University of Texas Southwestern, Dallas, Texas, USA
2Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA
Kaitlyn Saunders
1Department of Internal Medicine, Division of Hematology and Oncology, University of Texas Southwestern, Dallas, Texas, USA
2Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA
Sakshi Mohta
1Department of Internal Medicine, Division of Hematology and Oncology, University of Texas Southwestern, Dallas, Texas, USA
2Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA
Jacob Pena
1Department of Internal Medicine, Division of Hematology and Oncology, University of Texas Southwestern, Dallas, Texas, USA
2Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA
Heather L. McArthur
1Department of Internal Medicine, Division of Hematology and Oncology, University of Texas Southwestern, Dallas, Texas, USA
2Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA
Sangeetha M. Reddy
1Department of Internal Medicine, Division of Hematology and Oncology, University of Texas Southwestern, Dallas, Texas, USA
2Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA
Evanthia T. Roussos-Torres
6Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
Elizabeth H. Chen
2Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA
3Department of Molecular Biology, University of Texas Southwestern, Dallas, Texas, USA
4Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA
5Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA
Isaac S. Chan
1Department of Internal Medicine, Division of Hematology and Oncology, University of Texas Southwestern, Dallas, Texas, USA
2Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA
3Department of Molecular Biology, University of Texas Southwestern, Dallas, Texas, USA
4Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA
Abstract
Breast cancer metastases exhibit many different genetic alterations, including copy number amplifications. Using publicly available datasets, we identify copy number amplifications in metastatic breast tumor samples and using our organoid-based metastasis assays, and we validate FGFR1 is amplified in collectively migrating organoids. Because the heterogeneity of breast tumors is increasingly becoming relevant to clinical practice, we demonstrate our organoid method captures genetic heterogeneity of individual tumors.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Conflict of Interest Statement: No reported conflicts.
Copyright
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Posted January 31, 2023.
Organoid generation from mouse mammary tumors captures the genetic heterogeneity of clinically relevant copy number alterations
Katherine E. Lake, Megan M. Colonetta, Clayton A. Smith, Kenneth Martinez-Algarin, Kaitlyn Saunders, Sakshi Mohta, Jacob Pena, Heather L. McArthur, Sangeetha M. Reddy, Evanthia T. Roussos-Torres, Elizabeth H. Chen, Isaac S. Chan
bioRxiv 2023.01.29.526141; doi: https://doi.org/10.1101/2023.01.29.526141
Organoid generation from mouse mammary tumors captures the genetic heterogeneity of clinically relevant copy number alterations
Katherine E. Lake, Megan M. Colonetta, Clayton A. Smith, Kenneth Martinez-Algarin, Kaitlyn Saunders, Sakshi Mohta, Jacob Pena, Heather L. McArthur, Sangeetha M. Reddy, Evanthia T. Roussos-Torres, Elizabeth H. Chen, Isaac S. Chan
bioRxiv 2023.01.29.526141; doi: https://doi.org/10.1101/2023.01.29.526141
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