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

TY - JOUR

T1 - Challenges in Establishing Pure Lung Cancer Organoids Limit Their Utility for Personalized Medicine

AU - Dijkstra, Krijn K

AU - Monkhorst, Kim

AU - Schipper, Luuk J

AU - Hartemink, Koen J

AU - Smit, Egbert F

AU - Kaing, Sovann

AU - de Groot, Rosa

AU - Wolkers, Monika C

AU - Clevers, Hans

AU - Cuppen, Edwin

AU - Voest, Emile E

N1 - Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.

PY - 2020/5/5

Y1 - 2020/5/5

N2 - 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.

AB - 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.

U2 - 10.1016/j.celrep.2020.107588

DO - 10.1016/j.celrep.2020.107588

M3 - Article

C2 - 32375033

SN - 2211-1247

VL - 31

SP - 107588

JO - Cell Reports

JF - Cell Reports

IS - 5

ER -