采用靶向二代测序技术对低分化和间变性甲状腺癌进行突变分析。

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

机构信息

Department of Pathology, Molecular Pathology Research Centre, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.

Department of Pathology, National Cancer Centre/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

出版信息

Histopathology. 2019 Dec;75(6):890-899. doi: 10.1111/his.13942. Epub 2019 Oct 13.

DOI:10.1111/his.13942

PMID:31230400

Abstract

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 fusion. TERT and concurrent PIK3CA mutations predict worse overall survival in PDTC/ATC patients.

摘要

目的

分析低分化甲状腺癌（PDTC）和间变性甲状腺癌（ATC）的突变特征，并鉴定具有潜在诊断、预后和治疗意义的标志物。

方法和结果

对 41 例 PDTC 和 25 例 ATC 患者的组织样本进行了 18 个甲状腺癌相关基因的靶向下一代测序。还分析了遗传改变及其与临床病理因素（包括生存结果）的相关性。我们的结果显示，与 PDTC 相比，ATC 的 BRAF、TP53、TERT 和 PIK3CA 基因突变率明显更高（P=0.005、P=0.007、P=0.005 和 P=0.033）。9 例（69%）具有甲状腺乳头状癌（PTC）成分的 ATC 病例存在 BRAF 突变，所有这些突变均与晚期突变事件（TP53、TERT 或 PIK3CA）共存。在 41 例 PDTC 中发现了 9 例致癌融合（6 例 RET 病例、1 例 NTRK1 病例、1 例 ALK 病例和 1 例 PPARG 病例），而在 25 例 ATC 中仅发现 1 例致癌融合（NTRK1）。此外，所有 6 例 RET 融合均发生在具有 PTC 成分的 PDTC 中，占 33%。在 PDTC/ATC 患者中，在调整 TNM 分期后，TERT 和 PIK3CA 突变的同时存在与总生存期不良相关（P=0.001）。