Unidade de Investigação em Patobiologia Molecular (UIPM), Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG) E.P.E., Rua Prof. Lima Basto, 1099-023, Lisboa, Portugal.
Serviço de Endocrinologia, Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG) E.P.E., Rua Prof. Lima Basto, 1099-023, Lisboa, Portugal.
Endocrine. 2019 Nov;66(2):288-300. doi: 10.1007/s12020-019-02009-5. Epub 2019 Jul 31.
Anaplastic thyroid cancer (ATC) is among the most aggressive and unresectable tumors, presenting a bad prognosis. A better comprehension of the functional and molecular mechanisms behind the aggressiveness of this cancer, as well as new biomarkers for aggressiveness, prognosis, and response to therapy are required. However, owing to their irresectability, ATC tissue is not always accessible. Here we describe the establishment and characterization of a new patient-derived cell line, obtained from an unresectable ATC through fine-needle aspiration cytology (FNAC).
The morphology, expression of epithelial and thyroid markers, cytogenetic, mutational and gene expression profiles, doubling time, and drug-resistance profile of the new cell line, designated C3948, were investigated using several methodologies: immunostaining, karyotype analysis, comparative genomic hybridization (CGH), fluorescent in situ hybridization (FISH), next-generation sequencing (NGS), Sanger sequencing, gene expression microarrays, cell counting, and IC determination.
Results indicate that C3948 cell line has a histological phenotype representative of original ATC cells and a completely aberrant karyotype with many chromosomal losses and gains; harbors mutated TP53, STK11, and DIS3L2 genes; presents a gene expression profile similar to C643 ATC commercial cell line, but with some unique alterations; has a doubling time similar to C643; and the IC profile for paclitaxel, doxorubicin, and cisplatin is similar to C643, although higher for cisplatin.
These observations are consistent with a typical ATC cell profile, supporting C3948 cell line as a novel preclinical model, and FNAC as a useful approach to better study anaplastic thyroid cancer, including testing of new anticancer therapies.
间变性甲状腺癌（ATC）是最具侵袭性和不可切除的肿瘤之一，预后不良。需要更好地理解这种癌症侵袭性背后的功能和分子机制，以及新的侵袭性、预后和治疗反应的生物标志物。然而，由于其不可切除性，ATC 组织并不总是可获得的。在这里，我们描述了通过细针穿刺细胞学（FNAC）从不可切除的 ATC 中获得的新的患者来源细胞系的建立和特征。
使用多种方法研究了新的细胞系 C3948 的形态、上皮和甲状腺标志物的表达、细胞遗传学、突变和基因表达谱、倍增时间和耐药谱：免疫染色、核型分析、比较基因组杂交（CGH）、荧光原位杂交（FISH）、下一代测序（NGS）、Sanger 测序、基因表达微阵列、细胞计数和 IC 测定。
结果表明，C3948 细胞系具有代表原始 ATC 细胞的组织学表型和完全异常的核型，具有许多染色体缺失和增益；携带突变的 TP53、STK11 和 DIS3L2 基因；表现出与 C643 ATC 商业细胞系相似的基因表达谱，但具有一些独特的改变；倍增时间与 C643 相似；紫杉醇、多柔比星和顺铂的 IC 谱与 C643 相似，尽管顺铂的 IC 更高。
这些观察结果与典型的 ATC 细胞表型一致，支持 C3948 细胞系作为一种新的临床前模型，以及 FNAC 作为更好地研究间变性甲状腺癌的有用方法，包括测试新的抗癌疗法。
