Challenges in Establishing Pure Lung Cancer Organoids Limit Their Utility for Personalized Medicine
Dijkstra, Krijn K; Monkhorst, Kim; Schipper, Luuk J; Hartemink, Koen J; Smit, Egbert F; Kaing, Sovann; de Groot, Rosa; Wolkers, Monika C; Clevers, Hans; Cuppen, Edwin; Voest, Emile E
(2020) Cell Reports, volume 31, issue 5
(Article)
Abstract
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
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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.
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Keywords: genomics, non-small cell lung cancer, organoids, p63, personalized medicine, tumor purity, General Biochemistry,Genetics and Molecular Biology, Journal Article
ISSN: 2211-1247
Publisher: Cell Press
Note: Funding Information: We acknowledge Judith Westra, Sandra Visser, Louisa Hoes, Daphne van der Velden, Fleur Weeber, Xander Veenhof, and Houke Klomp for help with acquisition of patient tissue. We acknowledge the NKI-AVL Core Facility Molecular Pathology & Biobank (CFMPB) for supplying NKI-AVL Biobank material and lab support. Ron Kerkhoven, Marja Nieuwland, Roel Kluin, Charlaine Steenis, and Wim Brugman generated CN data for ITO41-T. We thank Chiara Cattaneo for support in organoid culture. This work was supported by the Dutch Cancer Society ( HUBR 2014-7006 ) and the NWO Gravitation Program (NWO; 2012-2022 ) (to E.E.V.). Funding Information: We acknowledge Judith Westra, Sandra Visser, Louisa Hoes, Daphne van der Velden, Fleur Weeber, Xander Veenhof, and Houke Klomp for help with acquisition of patient tissue. We acknowledge the NKI-AVL Core Facility Molecular Pathology & Biobank (CFMPB) for supplying NKI-AVL Biobank material and lab support. Ron Kerkhoven, Marja Nieuwland, Roel Kluin, Charlaine Steenis, and Wim Brugman generated CN data for ITO41-T. We thank Chiara Cattaneo for support in organoid culture. This work was supported by the Dutch Cancer Society (HUBR 2014-7006) and the NWO Gravitation Program (NWO; 2012-2022) (to E.E.V.). Conceptualization, K.K.D. E.F.S. E.C. H.C. and E.E.V.; Methodology, K.K.D. K.M. S.K. and E.C.; Investigation, K.K.D. and K.M.; Resources, L.J.S. K.J.H. E.F.S. S.K. R.G. and M.C.W.; Writing ? Original Draft, K.K.D.; Writing ? Review and Editing, K.M. L.J.S. K.J.H. E.F.S. M.C.W. E.C. and E.E.V.; Supervision, E.E.V.; Funding Acquisition, E.F.S. E.C. H.C. and E.E.V. H.C. declares the following management/advisory relationships: distinguished visiting professor, University of Hong Kong; member of the Scientific Advisory Board of Surrozen, San Francisco, California, USA; member of the Scientific Advisory Board of Kallyope, New York, USA; member of the Scientific Advisory Board of Merus, Utrecht, the Netherlands; scientific adviser to Life Science Partners, Amsterdam, the Netherlands; non-executive board member of Roche Holding Ltd. Basel, Switzerland. Publisher Copyright: © 2020 The Author(s)
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