Substantial intrinsic variability in chemoradiosensitivity of newly established anaplastic thyroid cancer cell-lines.

Background: Well characterized human cell lines are needed for preclinical treatment studies of anaplastic thyroid cancer (ATC). Aims/Objectives: The aim was to establish, verify and characterize a panel of ATC cell lines. Material and methods: Cell lines were established from ATC fine-needle aspiration biopsies and characterized genetically and functionally regarding treatment sensitivities. Results: Eight cell lines were established in vitro and the anaplastic thyroid origin was verified. Seven of the cell lines were also grown as xenografts. The cell lines harboured complex karyotypes with modal numbers in hyperdiploid to near-pentaploid range. Five were TP53 mutated and three carried the BRAFV600E mutation. None had rearrangements of RET. For doxorubicin, IC50 ranged from 0.42 to 46 nmol/L and for paclitaxel from 1.6 to 196 nmol/L. Radiation sensitivity varied between 2.6 and 6.3 Gy. Two of the BRAF mutated cell lines displayed high sensitivity to vemurafenib, while the third was similar to the wild-type ones. Conclusions and significance: We describe a series of new ATC cell lines demonstrating large heterogeneity in the response to cytostatic drugs and the BRAF inhibitor vemurafenib. The observations are relevant to future attempts to optimize treatment combinations for ATC. [ABSTRACT FROM AUTHOR]

背景：在间变性甲状腺癌（ATC）的临床前治疗研究中, 需要具有特性明确的人细胞系。 目的：建立和验证一组ATC细胞系, 并确定其特性。 材料和方法：从ATC细针穿刺活检组织中建立细胞系, 并就其治疗敏感性在基因和功能上确定细胞系的特性。 结果：体外建立了8个细胞系, 证实了间变性甲状腺起因。其中7个细胞系还作为异种移植物生长。这些细胞系具有复杂的核型, 其模式数在超二倍体到近五倍体范围之内。其中5例为TP53突变, 3例为BRAFV600E突变。无一例出现RET重排, 多柔比星IC50为0.42～46 nmol/L, 紫杉醇为1.6～196 nmol/L。放射敏感性为2.6～6.3Gy。其中两个BRAF突变细胞系对威罗菲尼（vemurafenib）表现出高度的敏感性, 而第三个与野生型细胞系相似。 结论和意义：我们描述了一系列新的ATC细胞系。它们对细胞抑制药物和BRAF抑制剂威罗菲尼的反应具有很大的异质性。这些观察结果与未来优化ATC治疗组合的尝试有关。 [ABSTRACT FROM AUTHOR]