Cell Reports
Volume 31, Issue 5, 5 May 2020, 107588
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Challenges in Establishing Pure Lung Cancer Organoids Limit Their Utility for Personalized Medicine

https://doi.org/10.1016/j.celrep.2020.107588Get rights and content
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Highlights

  • Frequent overgrowth of lung cancer organoids by normal airway organoids

  • Copy number profiling and IHC can be used to distinguish tumor and normal organoids

  • Low establishment rate of pure lung cancer organoids limits their clinical utility

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.

Keywords

organoids
personalized medicine
tumor purity
genomics
p63
non-small cell lung cancer

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