Vall d'Hebron Institute of Oncology (VHIO) Vall d'Hebron University Hospital, Barcelona.
Vall d Hebron Institute of Research (VHIR), Vall d'Hebron University Hospital, Barcelona.
Ann Oncol. 2018 Jun 1;29(6):1454-1460. doi: 10.1093/annonc/mdy123.
Papillary thyroid cancer (PTC) is the most common thyroid carcinoma and exhibits an almost uniformly good prognosis, while anaplastic thyroid cancer (ATC) is less frequent and is one of the most aggressive cancers usually resistant to conventional treatment. Current hypothesis posits that ATC derives from PTC through the progressive acquisition of a discrete number of genomic alterations and implies that the mutational landscape of ATC resembles that of PTC. However, the clinical behaviour of ATC and PTC is radically different. We decided to address the disconnection between the clinical behaviour of ATC and PTC and the proposed model of the progressive development of ATC from PTC.
We carried out exome sequencing of DNA from 14 ATC specimens including three cases of concomitant ATC and PTC as well as their corresponding normal DNA from 14 patients. The sequencing results were validated using droplet digital PCR. We carried out immunohistochemistry and immunofluorescence studies of the concomitant ATC and PTC cases. In addition, we integrated our sequencing results with the existing TCGA data.
Most of the somatic mutations identified in the ATC component differed from the ones in PTC in the cases of concomitant ATC and PTC. The trunks of the phylogenetic trees representing the somatic mutations were short with long branches. In one case of concomitant PTC and ATC specimens, we observed an infiltration of PTC cells within the ATC component. Moreover, we integrated our results with data obtained from TCGA and observed that the most frequent mutations found in ATC presented high cancer cell fraction values and were significantly different from the PTC ones.
ATC diverge from PTC early in tumour development and both tumour types evolve independently. Our work allows the understanding of the relationship between ATC and PTC facilitating the clinical management of these malignancies.
甲状腺乳头状癌（PTC）是最常见的甲状腺癌，几乎普遍预后良好，而间变性甲状腺癌（ATC）则较少见，是最具侵袭性的癌症之一，通常对常规治疗有抗性。目前的假说认为 ATC 是通过逐步获得离散数量的基因组改变从 PTC 衍生而来的，这意味着 ATC 的突变景观类似于 PTC。然而，ATC 和 PTC 的临床行为却截然不同。我们决定解决 ATC 和 PTC 的临床行为之间以及 ATC 从 PTC 逐渐发展的提议模型之间的脱节问题。
我们对来自 14 名患者的 14 个 ATC 标本的 DNA 进行了外显子组测序，其中包括三个同时存在 ATC 和 PTC 的病例及其相应的正常 DNA。使用液滴数字 PCR 验证了测序结果。我们对同时存在的 ATC 和 PTC 病例进行了免疫组织化学和免疫荧光研究。此外，我们将测序结果与现有的 TCGA 数据进行了整合。
在同时存在 ATC 和 PTC 的病例中，ATC 成分中鉴定出的大多数体细胞突变与 PTC 中的突变不同。代表体细胞突变的系统发育树的树干很短，分支很长。在一个同时存在 PTC 和 ATC 标本的病例中，我们观察到 PTC 细胞在 ATC 成分内浸润。此外，我们将我们的结果与从 TCGA 获得的数据进行了整合，并观察到在 ATC 中发现的最常见突变具有高癌细胞分数值，与 PTC 明显不同。
ATC 在肿瘤发展早期就与 PTC 分化，两种肿瘤类型独立进化。我们的工作允许理解 ATC 和 PTC 之间的关系，从而促进这些恶性肿瘤的临床管理。
