目的:对甲状腺乳头状癌(PTCs)和低分化甲状腺癌(PDTC)的转移进行分子谱分析。
方法:我们检索并分析了136个来自PTC的转移和35个来自PDTC的转移的分子和临床特征,来自cBioPortal。临床病理数据包括转移灶的数量和位置,基因组数据包括突变,易位,拷贝数改变和基因组改变比例(FGA)。
结果:PTC骨转移的BRAF突变频率低于淋巴结转移(LNMs)(43%vs88%,p<0.01),RBM10和NRAS突变的频率高于LNM(两者均为21%对3%,p<0.05)。骨转移的FGA高于肺转移的FGA(5.6%vs1.3%,p<0.05)。在来自PTC的肺转移中,RET易位的频率高于LNM(15%对3%,p<0.05)。携带4个或更多远处转移(DMs)的PTC患者的LNM比携带少于4个DMs的患者的LNM具有更高的TERT启动子突变频率(96%vs65%,p<0.001)。SDHA基因扩增在PDTC的骨转移中富集,而在LNM中不存在(38%vs0%,p<0.05)。
结论:来自PTC和PDTC的转移有影响不同身体位置的临床相关改变,如NRAS和RBM10突变,RET易位和SDHA扩增可用于治疗。
OBJECTIVE: To perform a molecular profiling of the metastases from papillary thyroid carcinomas (PTCs) and poorly differentiated thyroid carcinomas (PDTCs).
METHODS: We retrieved and analyzed the molecular and clinical features of 136 metastases from PTCs and 35 metastases from PDTCs subjected to targeted DNA sequencing, from cBioPortal. The clinicopathological data included the number and location of the metastases, and genomic data included mutations, translocations, copy number alterations and fraction of the genome altered (FGA).
RESULTS: Bone metastases from PTCs had a lower frequency of BRAF mutations than the lymph node metastases (LNMs) (43% vs 88%, p < 0.01), and a higher frequency of RBM10 and NRAS mutations than the LNMs (21% vs 3% for both, p < 0.05). The FGA of the bone metastases was higher than the FGA of the lung metastases (5.6% vs 1.3%, p < 0.05). The frequency of RET translocations was higher in the lung metastases from PTCs than the LNMs (15% vs 3%, p < 0.05). The LNMs from PTC patients harboring 4 or more distant metastases (DMs) had a higher frequency of TERT promoter mutations than the LNMs from patients harboring less than 4 DMs (96% vs 65%, p < 0.001). SDHA gene amplifications were enriched in the bone metastases from PDTCs and absent in the LNMs (38% vs 0%, p < 0.05).
CONCLUSIONS: Metastases from PTCs and PDTCs harbor clinically relevant alterations affecting distinct body locations, such as NRAS and RBM10 mutations, RET translocations and SDHA amplifications that may be explored therapeutically.