Establishment and characterization of novel human primary and metastatic anaplastic thyroid cancer (ATC) cell lines and their genomic evolution over a year as a primagraft

Context: Anaplastic thyroid cancer (ATC) has no effective treatment, resulting in high rate of mortality. We established cell lines from a primary ATC and its lymph node metastasis, and investigated the molecular factors and genomic changes associated with tumor growth. Objective: The aim of the study was to understand the molecular and genomic changes of highly aggressive ATC and its clonal evolution to develop rational therapies. Design: We established unique cell lines from primary (OGK-P) and metastatic (OGK-M) ATC specimen, as well as primagraft from the metastatic ATC which was serially xeno-transplanted for more than one year in NSG mice were established. These cell lines and primagraft were used as tools to examine gene expression, copy number changes and somatic mutations using RNA array, SNP Chip and whole exome sequencing.

研究背景：间变性甲状腺癌（Anaplastic Thyroid Cancer, ATC）目前尚无有效的临床治疗手段，患者致死率极高。本研究从1例原发性间变性甲状腺癌及其淋巴结转移灶中成功构建细胞系，旨在探究与肿瘤生长相关的分子调控因子及基因组改变。
研究目的：本研究旨在明确高侵袭性间变性甲状腺癌的分子与基因组特征及其克隆进化机制，为制定合理的靶向治疗策略提供理论基础。
实验设计：我们分别从原发性间变性甲状腺癌标本（OGK-P）与转移性间变性甲状腺癌标本（OGK-M）中构建了专属细胞系；同时构建了转移性间变性甲状腺癌原代异种移植物，该移植物已在NSG小鼠中连续异种传代超过1年。本研究以这些细胞系及原代异种移植物为实验工具，通过RNA阵列（RNA array）、SNP芯片（SNP Chip）及全外显子组测序（whole exome sequencing）检测基因表达水平、拷贝数变异及体细胞突变。