Challenges in Establishing Pure Lung Cancer Organoids Limit Their Utility for Personalized Medicine

Cell Reports

Emile E. Voest¹  Egbert F. Smit²  Hans Clevers²  Kim Monkhorst²  Edwin Cuppen³  Krijn K. Dijkstra⁴  Monika C. Wolkers⁴  Koen J. Hartemink⁴  Luuk J. Schipper⁵  Sovann Kaing⁶  Rosa de Groot⁷ 

[1] Landsteiner Laboratory, Amsterdam University Medical Center, Location AMC, 1105 AZ Amsterdam, the Netherlands;Oncode Institute, Utrecht, the Netherlands;Department of Hematopoiesis, Sanquin Research, 1066 CX Amsterdam, the Netherlands;Department of Molecular Oncology and Immunology, the Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, 1066 CX Amsterdam, the Netherlands;Department of Pathology, the Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, 1066 CX Amsterdam, the Netherlands;Department of Surgery, the Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, 1066 CX Amsterdam, the Netherlands;Department of Thoracic Oncology, the Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, 1066 CX Amsterdam, the Netherlands;

关键词: organoids;    personalized medicine;    tumor purity;    genomics;    p63;    non-small cell lung cancer;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown