BRAF and TERT promoter mutations in the aggressiveness of papillary thyroid carcinoma: a study of 653 patients.
BRAF and TERT promoter mutations in the aggressiveness of papillary thyroid carcinoma: a study of 653 patients.
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DOI：
10.18632/oncotarget.7811
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发表时间：
2016-04-05
期刊：
影响因子：
--
通讯作者：
Wang O
中科院分区：
文献类型：
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作者：
Jin L;Chen E;Dong S;Cai Y;Zhang X;Zhou Y;Zeng R;Yang F;Pan C;Liu Y;Wu W;Xing M;Zhang X;Wang O
端粒酶逆转录酶（TERT）基因启动子突变在甲状腺乳头状癌（PTC）侵袭性中的作用仍有待进一步研究。在这里，我们检查了 653 名患者的 TERT 启动子突变和 BRAF V600E 与 PTC 临床病理特征的关系。对原发性 PTC 肿瘤的基因组 DNA 进行 Sanger 测序以检测突变，并分析肿瘤的基因型与临床病理学相关性。分别在 63.7%（653 名患者中的 416 名）和 4.1%（653 名患者中的 27 名）患者中发现 BRAF V600E 和 TERT 启动子突变；当仅分析≥1.5cm的肿瘤时，后者变为9.8%。与野生型病例相比，BRAF 突变阳性病例中 TERT 启动子突变发生的频率更高，前者为 5.3%，后者为 2.1%（P = 0.050）。 BRAF和TERT启动子突变均与PTC的高危临床病理特征显着相关，例如患者年龄大、肿瘤体积大、甲状腺外侵犯、包膜侵犯和晚期疾病阶段。 BRAF V600E 和 TERT 启动子突变的共存与高风险临床病理特征尤其相关，例如，在携带这两种突变的患者中，54.5% (12/22) 的患者出现甲状腺外侵犯，而在不携带任何突变的患者中，这一比例为 9.9% (23/232) (P < 0.001)。因此，这项迄今为止规模最大的 TERT 突变研究证明了 BRAF V600E 和 TERT 启动子突变在 PTC 侵袭性中的重要作用，当两种突变共存时，这种作用尤其强大和协作。这些结果与之前的研究一起确定了这些突变在 PTC 的侵袭性中发挥着重要作用。
The role of telomerase reverse transcriptase (TERT) gene promoter mutations in the aggressiveness of papillary thyroid cancer (PTC) remains to be further investigated. Here we examined the relationship of TERT promoter mutations and BRAF V600E with the clinicopathological features of PTC in 653 patients. Sanger sequencing of genomic DNA from primary PTC tumors was performed for mutation detection and genotype-clinicopathological correlation of the tumor was analyzed. BRAF V600E and TERT promoter mutations were found in 63.7% (416 of 653) and 4.1% (27 of 653) of patients, respectively; the latter became 9.8% when only tumors ≥ 1.5 cm were analyzed. TERT promoter mutations occurred more frequently in BRAF mutation-positive cases compared to wild-type cases, being 5.3% in the former versus 2.1% in the latter (P = 0.050). BRAF and TERT promoter mutations were each significantly associated with high-risk clinicopathological features of PTC, such as old patient age, large tumor size, extrathyroidal invasion, capsular invasion, and advanced disease stages. Coexistence of BRAF V600E and TERT promoter mutations was particularly associated with high-risk clinicopathological features, as exemplified by extrathyroidal invasion seen in 54.5% (12/22) of patients harboring both mutations versus 9.9% (23/232) of patients harboring neither mutation (P < 0.001). Thus, this study, the largest on TERT mutation so far, demonstrates a significant role of BRAF V600E and TERT promoter mutations in the aggressiveness of PTC, which is particularly robust and cooperative when the two mutations coexist. These results, together with previous studies, establish a significant role of these mutations in the aggressiveness of PTC.