Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar.
Institute of Pathology.
JCI Insight. 2020 Aug 6;5(15):137809. doi: 10.1172/jci.insight.137809.
One of the major challenges in using pancreatic cancer patient-derived organoids (PDOs) in precision oncology is the time from biopsy to functional characterization. This is particularly true for endoscopic ultrasound-guided fine-needle aspiration biopsies, typically resulting in specimens with limited tumor cell yield. Here, we tested conditioned media of individual PDOs for cell-free DNA to detect driver mutations already early on during the expansion process to accelerate the genetic characterization of PDOs as well as subsequent functional testing. Importantly, genetic alterations detected in the PDO supernatant, collected as early as 72 hours after biopsy, recapitulate the mutational profile of the primary tumor, indicating suitability of this approach to subject PDOs to drug testing in a reduced time frame. In addition, we demonstrated that this workflow was practicable, even in patients for whom the amount of tumor material was not sufficient for molecular characterization by established means. Together, our findings demonstrate that generating PDOs from very limited biopsy material permits molecular profiling and drug testing. With our approach, this can be achieved in a rapid and feasible fashion with broad implications in clinical practice.
使用胰腺癌患者衍生类器官（PDO）进行精准肿瘤学研究的主要挑战之一是从活检到功能特征分析的时间。对于内镜超声引导下的细针抽吸活检尤其如此，通常导致标本中肿瘤细胞产量有限。在这里，我们测试了个体 PDO 的条件培养基中的无细胞 DNA，以在扩增过程中尽早检测驱动基因突变，从而加速 PDO 的遗传特征分析以及后续的功能测试。重要的是，在活检后 72 小时即可收集 PDO 上清液中检测到的遗传改变，重现了原发肿瘤的突变谱，表明该方法适用于在更短的时间内对 PDO 进行药物测试。此外，我们证明了即使对于肿瘤组织量不足以通过现有方法进行分子特征分析的患者，该工作流程也是可行的。总之，我们的研究结果表明，即使从非常有限的活检材料中生成 PDO，也可以进行分子分析和药物测试。通过我们的方法，可以快速且可行地实现这一目标，这在临床实践中具有广泛的意义。
