Challenges in Establishing Pure Lung Cancer Organoids Limit Their Utility for Personalized Medicine
Summary: Clinical implementation of tumor organoids for personalized medicine requires that pure tumor organoids can be reliably established. Here, we present our experience with organoid cultures from >70 non-small cell lung cancer (NSCLC) samples. We systematically evaluate several methods to i...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-05-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124720305374 |
| _version_ | 1828495373964935168 |
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| author | Krijn K. Dijkstra Kim Monkhorst Luuk J. Schipper Koen J. Hartemink Egbert F. Smit Sovann Kaing Rosa de Groot Monika C. Wolkers Hans Clevers Edwin Cuppen Emile E. Voest |
| author_facet | Krijn K. Dijkstra Kim Monkhorst Luuk J. Schipper Koen J. Hartemink Egbert F. Smit Sovann Kaing Rosa de Groot Monika C. Wolkers Hans Clevers Edwin Cuppen Emile E. Voest |
| author_sort | Krijn K. Dijkstra |
| collection | DOAJ |
| description | Summary: Clinical implementation of tumor organoids for personalized medicine requires that pure tumor organoids can be reliably established. Here, we present our experience with organoid cultures from >70 non-small cell lung cancer (NSCLC) samples. We systematically evaluate several methods to identify tumor purity of organoids established from intrapulmonary tumors. Eighty percent of organoids from intrapulmonary lesions have a normal copy number profile, suggesting overgrowth by normal airway organoids (AOs). This is further supported by the failure to detect mutations found in the original tumor in organoids. Histomorphology alone is insufficient to determine tumor purity, but when combined with p63 immunostaining, tumor and normal AOs can be distinguished. Taking into account overgrowth by normal AOs, the establishment rate of pure NSCLC organoids is 17%. Therefore, current methods are insufficient to establish pure NSCLC organoids from intrapulmonary lesions. We discourage their use unless steps are taken to prevent overgrowth by normal AOs. |
| first_indexed | 2024-12-11T12:12:07Z |
| format | Article |
| id | doaj.art-b469827b6c1c427c86f583c772baa165 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-11T12:12:07Z |
| publishDate | 2020-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-b469827b6c1c427c86f583c772baa1652022-12-22T01:07:46ZengElsevierCell Reports2211-12472020-05-01315Challenges in Establishing Pure Lung Cancer Organoids Limit Their Utility for Personalized MedicineKrijn K. Dijkstra0Kim Monkhorst1Luuk J. Schipper2Koen J. Hartemink3Egbert F. Smit4Sovann Kaing5Rosa de Groot6Monika C. Wolkers7Hans Clevers8Edwin Cuppen9Emile E. Voest10Department of Molecular Oncology and Immunology, the Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, 1066 CX Amsterdam, the Netherlands; Oncode Institute, Utrecht, the NetherlandsDepartment of Pathology, the Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, 1066 CX Amsterdam, the NetherlandsDepartment of Molecular Oncology and Immunology, the Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, 1066 CX Amsterdam, the Netherlands; Oncode Institute, Utrecht, the NetherlandsDepartment of Surgery, the Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, 1066 CX Amsterdam, the NetherlandsDepartment of Thoracic Oncology, the Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, 1066 CX Amsterdam, the NetherlandsDepartment of Molecular Oncology and Immunology, the Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, 1066 CX Amsterdam, the Netherlands; Oncode Institute, Utrecht, the NetherlandsDepartment of Hematopoiesis, Sanquin Research, 1066 CX Amsterdam, the Netherlands; Landsteiner Laboratory, Amsterdam University Medical Center, Location AMC, 1105 AZ Amsterdam, the Netherlands; Oncode Institute, Utrecht, the NetherlandsDepartment of Hematopoiesis, Sanquin Research, 1066 CX Amsterdam, the Netherlands; Landsteiner Laboratory, Amsterdam University Medical Center, Location AMC, 1105 AZ Amsterdam, the Netherlands; Oncode Institute, Utrecht, the NetherlandsHubrecht Institute, University Medical Center Utrecht, 3584 CT Utrecht, the Netherlands; Princess Maxima Center for Pediatric Oncology, 3584 CS Utrecht, the Netherlands; Oncode Institute, Utrecht, the NetherlandsCentre for Molecular Medicine, University Medical Centre Utrecht, 3584 CG Utrecht, the Netherlands; Hartwig Medical Foundation, 1098 XH Amsterdam, the Netherlands; Oncode Institute, Utrecht, the NetherlandsDepartment of Molecular Oncology and Immunology, the Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, 1066 CX Amsterdam, the Netherlands; Oncode Institute, Utrecht, the Netherlands; Corresponding authorSummary: Clinical implementation of tumor organoids for personalized medicine requires that pure tumor organoids can be reliably established. Here, we present our experience with organoid cultures from >70 non-small cell lung cancer (NSCLC) samples. We systematically evaluate several methods to identify tumor purity of organoids established from intrapulmonary tumors. Eighty percent of organoids from intrapulmonary lesions have a normal copy number profile, suggesting overgrowth by normal airway organoids (AOs). This is further supported by the failure to detect mutations found in the original tumor in organoids. Histomorphology alone is insufficient to determine tumor purity, but when combined with p63 immunostaining, tumor and normal AOs can be distinguished. Taking into account overgrowth by normal AOs, the establishment rate of pure NSCLC organoids is 17%. Therefore, current methods are insufficient to establish pure NSCLC organoids from intrapulmonary lesions. We discourage their use unless steps are taken to prevent overgrowth by normal AOs.http://www.sciencedirect.com/science/article/pii/S2211124720305374organoidspersonalized medicinetumor puritygenomicsp63non-small cell lung cancer |
| spellingShingle | Krijn K. Dijkstra Kim Monkhorst Luuk J. Schipper Koen J. Hartemink Egbert F. Smit Sovann Kaing Rosa de Groot Monika C. Wolkers Hans Clevers Edwin Cuppen Emile E. Voest Challenges in Establishing Pure Lung Cancer Organoids Limit Their Utility for Personalized Medicine Cell Reports organoids personalized medicine tumor purity genomics p63 non-small cell lung cancer |
| title | Challenges in Establishing Pure Lung Cancer Organoids Limit Their Utility for Personalized Medicine |
| title_full | Challenges in Establishing Pure Lung Cancer Organoids Limit Their Utility for Personalized Medicine |
| title_fullStr | Challenges in Establishing Pure Lung Cancer Organoids Limit Their Utility for Personalized Medicine |
| title_full_unstemmed | Challenges in Establishing Pure Lung Cancer Organoids Limit Their Utility for Personalized Medicine |
| title_short | Challenges in Establishing Pure Lung Cancer Organoids Limit Their Utility for Personalized Medicine |
| title_sort | challenges in establishing pure lung cancer organoids limit their utility for personalized medicine |
| topic | organoids personalized medicine tumor purity genomics p63 non-small cell lung cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2211124720305374 |
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