甲状腺未分化癌（ATC）恶性程度极高，中位生存期仅5个月，文献报道14-50%的甲状腺癌相关的死亡是由ATC或者乳头状癌（PTC）的去分化造成的，因此系统研究ATC的发病机制将会全面提高甲状腺癌的诊治结果。但由于ATC发病率较低、研究样本的缺乏使得ATC的研究长期处于将其他肿瘤研究结果在ATC验证的状态。申请者所在单位应用多学科协作的模式将ATC的中位生存期延长至9个月，积累了一定临床资源，前期对5例样本的深度测序分析显示ATC有独特的基因突变谱、转录组、融合基因和lncRNA表达谱，同时每个病例都有可以被小分子抑制剂靶向的激酶基因突变。本课题将继续应用全基因组和转录组测序的方法，进行ATC的分子分型；对ATC细胞系进行分子分型为基础的靶向药物实验，建立用药指导；应用整合基因组分析方法，比较PTC与ATC的异同，筛选PTC去分化的分子标记，课题将全面提高ATC以及PTC的诊治水平。

Anaplastic thyroid cancer (ATC) is one of the most aggressive cancer types with the median survival time of 5 months. About 14-50% of thyroid cancer related death was accounted to ATC and the dedifferentiation of papillary thyroid cancer (PTC). The systematic evaluation of pathogenesis of ATC will improve the level of diagnosis and treatment of thyroid cancer. Due to the lower incidence and advanced stage of ATC, the samples of ATC for research are limited. Most of researches of ATC are the validation of the results of other cancer types. The applicant and his hospital use the multi-discipline management of ATC and improve the median survival time of ATC to 9 months and have collected a lot of clinical samples. The whole exome sequencing of ATC showed that the ATC have different gene mutation panel, mRNA expression panel, gene fusion and lncRNA panel. Every ATC case has kinases mutation which could be targeted by small molecular inhibitors. The whole genome sequencing and transcriptome sequencing will be used for molecular classification of ATC in current research project. The usage of target drugs based on the typing of molecular classification of ATC will be tested in ATC cell lines, and the guideline of drugs used will be drawn. The differences of ATC and PTC will be compared by integrated genome analysis of ATC and PTC data. The biomarkers for detecting the dedifferentiation possibility of PTC will be founded. This project will improve the diagnosis and treatment of ATC and PTC.