Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.
Department of Clinical Pharmacy, School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, Liaoning, China.
Cancer Biomark. 2020;27(4):445-460. doi: 10.3233/CBM-191200.
To characterize the somatic alterations of papillary thyroid carcinomas (PTC) in Chinese patients, we performed the next-generation-sequencing (NGS) study of the tumor-normal pairs of DNA and RNA samples extracted from 16 Chinese PTC patients. The whole genome sequencing (WGS) and transcriptome sequencing (RNA-seq) were conducted for 6 patients who were either current or former smokers and the whole exome sequencing (WES) and RNA-seq were conducted for another 10 patients who were never smokers. The NGS data were analyzed to identify somatic alteration events that may underlie PTC in Chinese patients. We identified a number of PTC driver genes harboring somatic driver mutations with significant functional impact such as COL11A1, TP53, PLXNA4, UBA1, AHNAK, CSMD2 and TTLL5 etc. Significant driver pathways underlying PTC were found, namely, the metabolic pathway, the pathway in cancer, the olfactory transduction pathway and the calcium signaling pathway. In addition, this study revealed genes with significant somatic copy number aberrations and corresponding somatic gene expression changes in PTC tumors, the most promising ones being BRD9, TRIP13, FZD3, and TFDP1 etc. We also identified several structural variants of PTCs, especially the novel in-frame fusion proteins such as TRNAU1AP-RCC1, RAB3GAP1-R3HDM1, and ENAH-ZSWIM5. Our study provided a list of novel PTC candidate genes with somatic alterations that may function as biomarkers for PTC in Chinese patients. The follow-up mechanism studies may be conducted based on the findings from this study.
为了研究中国人群甲状腺乳头状癌（PTC）的体细胞改变，我们对 16 例中国 PTC 患者的肿瘤-正常 DNA 和 RNA 样本进行了下一代测序（NGS）研究。对 6 例现吸烟或既往吸烟患者进行了全基因组测序（WGS）和转录组测序（RNA-seq），对 10 例从不吸烟患者进行了全外显子组测序（WES）和 RNA-seq。对 NGS 数据进行分析，以确定可能导致中国人群 PTC 的体细胞改变事件。我们鉴定了一些 PTC 驱动基因，这些基因携带有显著功能影响的体细胞驱动突变，如 COL11A1、TP53、PLXNA4、UBA1、AHNAK、CSMD2 和 TTLL5 等。发现了一些 PTC 的重要驱动途径，包括代谢途径、癌症途径、嗅觉转导途径和钙信号转导途径。此外，本研究揭示了 PTC 肿瘤中具有显著体细胞拷贝数异常和相应体细胞基因表达变化的基因，最有希望的基因包括 BRD9、TRIP13、FZD3 和 TFDP1 等。我们还鉴定了一些 PTC 的结构变异，特别是新型的框架内融合蛋白，如 TRNAU1AP-RCC1、RAB3GAP1-R3HDM1 和 ENAH-ZSWIM5。本研究提供了一份中国人群 PTC 体细胞改变的候选基因列表，这些基因可能作为 PTC 的生物标志物。可以根据本研究的结果进行后续的机制研究。
