Mutational profiling of poorly differentiated and anaplastic thyroid carcinoma by the use of targeted next‐generation sequencing

作者：Huanli Duan, Yan Li, Peizhen Hu, Jie Gao, Jianming Ying, Wanni Xu, Danhui Zhao, Zhe Wang, Junyi Ye, Analyn Lizaso, Yangzhige He, Huanwen Wu, Zhiyong Liang · 发表于：Histopathology · 年份：2019 · DOI：10.1111/his.13942 · 被引用次数：93 · 研究领域：Thyroid Cancer Diagnosis and Treatment、BRCA gene mutations in cancer、Genetic factors in colorectal cancer

AIMS: To characterise the mutational profiles of poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC) and to identify markers with potential diagnostic, prognostic and therapeutic significance. METHODS AND RESULTS: Targeted next-generation sequencing with a panel of 18 thyroid carcinoma-related genes was performed on tissue samples from 41 PDTC and 25 ATC patients. Genetic alterations and their correlations with clinicopathological factors, including survival outcomes, were also analysed. Our results showed that ATC had significantly higher mutation rates of BRAF, TP53, TERT and PIK3CA than PDTC (P = 0.005, P = 0.007, P = 0.005, and P = 0.033, respectively). Nine (69%) ATC cases with papillary thyroid carcinoma (PTC) components harboured BRAF mutations, all of which coexisted with a late mutation event (TP53, TERT, or PIK3CA). Nine cases with oncogenic fusion (six RET cases, one NTRK1 case, one ALK case, and one PPARG case) were identified in 41 PDTCs, whereas only one case with oncogenic fusion (NTRK1) was found among 25 ATCs. Moreover, all six cases of RET fusion were found in PDTC with PTC components, accounting for 33%. In PDTC/ATC patients, concurrent TERT and PIK3CA mutations were associated with poor overall survival after adjustment for TNM stage (P = 0.001). CONCLUSIONS: ATC with PTC components is typically characterised by a BRAF mutation with a late mutation event, whereas PDTC with PTC components is more closely correlated with RET...