TERT, BRAF, and NRAS in Primary Thyroid Cancer and Metastatic Disease
TERT, BRAF, and NRAS in Primary Thyroid Cancer and Metastatic Disease
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DOI：
10.1210/jc.2016-2785
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发表时间：
2017-06-01
影响因子：
5.8
通讯作者：
Soares, Paula
中科院分区：
文献类型：
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作者：
Melo, Miguel;da Rocha, Adriana Gaspar;Soares, Paula
背景：关于甲状腺癌转移的关键突变频率及其与原发肿瘤基因型的关系知之甚少。目的：评估转移性甲状腺癌中TERT启动子（TERTp）、BRAF和NRAS突变的频率，分析原发性甲状腺肿瘤、淋巴结转移（LNMs）和远处转移。设计和患者：对204例患者的437份组织样本进行突变分析，主要是甲状腺乳头状癌（ptc, n = 180），包括196例LNMs和56例远处转移。所有远处转移灶均为放射性碘难治性转移组织。结果：我们发现原发性ptc、LNMs和远处转移的突变频率分别为：TERTp: 12.9%、10.5%和52.4%；BRAF: 44.6%、41.7%和23.8%；NRAS: 1.2%， 1.3%和14.3%。所有基因的原发肿瘤基因型与相应的LNM之间存在显著的一致性，尤其是braf突变的PTC。原发肿瘤与各自远处转移的总体一致性较低。在ptc患者组中，与配对的原发肿瘤相比，我们发现远端转移的TERTp突变频率高，BRAF突变频率低。当存在于远处转移时，BRAF突变经常与TERTp突变共存。结论：将原发性肿瘤的基因型与LNMs的基因型进行比较，所有基因的一致性都很高。另一方面，远端转移表现出TERTp突变的富集和BRAF突变的减少。TERTp突变可能在远处转移中起作用。
Context: Little is known about the frequency of key mutations in thyroid cancer metastases and its relationship with the primary tumor genotype.Objectives: To evaluate the frequency of TERT promoter (TERTp), BRAF, and NRAS mutations in metastatic thyroid carcinomas, analyzing primary thyroid tumors, lymphnode metastases (LNMs), and distant metastases.Design and Patients: Mutation analysis was performed in 437 tissue samples from 204 patients, mainly with papillary thyroid carcinomas (PTCs; n = 180), including 196 LNMs and 56 distant metastases. All the distant metastases included corresponded to radioiodine-refractory metastatic tissue.Results: We found the following mutation frequency in primary PTCs, LNMs, and distant metastases, respectively: TERTp: 12.9%, 10.5%, and 52.4%; BRAF: 44.6%, 41.7%, and 23.8%; and NRAS: 1.2%, 1.3%, and 14.3%. There was a significant concordance between the primary tumor genotype and the corresponding LNM for all the genes, in particular BRAF-mutated PTC. The overall concordance between primary tumors and respective distant metastases was low. In the group of patients with PTCs, we found a high frequency of TERTp mutations and a low frequency of BRAF mutations in distant metastases, in comparison with the paired primary tumors. When present in distant metastases, BRAF mutations frequently coexisted with TERTp mutations.Conclusions: When the genotype of primary tumors is compared with the genotype of LNMs, the concordance is high for all the genes studied. On the other hand, distant metastases show an enrichment in TERTp mutations and a decrease in BRAF mutations. TERTp mutations may play a role in distant metastases.