患者来源唾液腺癌类器官培养的开发和特性研究。
Development and characterization of patient-derived salivary gland cancer organoid cultures.
机构信息
Department of Medical Oncology, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
Department of Urology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
出版信息
Oral Oncol. 2022 Dec;135:106186. doi: 10.1016/j.oraloncology.2022.106186. Epub 2022 Oct 18.
OBJECTIVE
Three-dimensional organoid cell cultures have been established for a variety of human cancers. For most rare cancers, including salivary gland cancer (SGC), these models are lacking, despite the great unmet need to study cancer biology in these diseases. Therefore, we aimed to develop patient-derived organoid (PDO) models for different subtypes of SGC.
METHODS
Tumor samples of SGC patients were processed and embedded in Matrigel. Successful PDOs (expandable > 1*10 cells) were phenotypically characterized using immunohistochemistry (IHC) and genotypically by gene fusion analysis and by targeted and whole-exome sequencing. Successfully established PDOs were subjected to small-scale drug screening.
RESULTS
Out of 37 attempts, 7 viable short-term PDOs were established (19 % success rate; 3 salivary duct carcinoma, 3 adenoid cystic carcinoma and 1 mucoepidermoid carcinoma). Each PDO showed close phenotypical mimicry to parental tissue. Genotypic characterization revealed that in each PDO > 97.6 % of all COSMIC annotated variants and all MYB, MYBL1 and NFIB gene rearrangements were retained. Drug screening was proven feasible in all PDOs.
CONCLUSION
We present the first comprehensively characterized short-term SGC PDO models for three subtypes of SGC with close phenotypic and genotypic resemblance to parental tissue, which can be used for drug screening applications.
目的
已建立多种人类癌症的三维类器官细胞培养物。对于大多数罕见癌症，包括唾液腺癌（SGC），尽管非常需要研究这些疾病中的癌症生物学，但这些模型仍然缺乏。因此，我们旨在为不同亚型的 SGC 开发患者来源的类器官（PDO）模型。
方法
对 SGC 患者的肿瘤样本进行处理并嵌入 Matrigel 中。使用免疫组织化学（IHC）对成功的 PDO（可扩展> 1*10 个细胞）进行表型特征分析，并通过基因融合分析以及靶向和全外显子组测序进行基因分析。成功建立的 PDO 进行了小规模药物筛选。
结果
在 37 次尝试中，建立了 7 个可行的短期 PDO（成功率为 19%；3 个唾液管癌，3 个腺样囊性癌和 1 个粘液表皮样癌）。每个 PDO 均表现出与亲本组织密切的表型模拟。基因特征分析显示，在每个 PDO 中，所有 COSMIC 注释变体和所有 MYB、MYBL1 和 NFIB 基因重排的> 97.6%都被保留。所有 PDO 均证明药物筛选可行。
结论
我们首次全面描述了三种 SGC 亚型的短期 SGC PDO 模型，它们与亲本组织具有密切的表型和基因相似性，可用于药物筛选应用。
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