Mutations of TSHR and TP53 Genes in an Aggressive Clear Cell Follicular Carcinoma of the Thyroid
Mutations of TSHR and TP53 Genes in an Aggressive Clear Cell Follicular Carcinoma of the Thyroid
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DOI：
10.1007/s12022-015-9388-1
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发表时间：
2015-08
影响因子：
4.4
通讯作者：
G. Tong;K. Mody;Zhuo-cai Wang;D. Hamele-Bena;M. Nikiforova;Y. Nikiforov
中科院分区：
文献类型：
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作者：
G. Tong;K. Mody;Zhuo-cai Wang;D. Hamele-Bena;M. Nikiforova;Y. Nikiforov
透明细胞滤泡癌是一种罕见的甲状腺癌，有些具有侵袭性生物学行为。肿瘤细胞的胞质清除归因于各种物质的积累，如糖原、脂质、粘蛋白和甲状腺球蛋白，或线粒体或内质网的扩张。然而，负责细胞质的特征外观和生物学行为的分子机制仍然未知。我们在这里报告的情况下，积极透明细胞滤泡癌的甲状腺与分子概况使用靶向下一代测序（NGS），提出了作为一个转移性肿瘤的妇女与乳腺癌的历史。NGS结果显示，该肿瘤中同时存在TP53 R248Q突变和TSHR L272V突变，这与甲状腺球蛋白和SLC5A5（NIS）基因的过度表达有关，TP53突变通常与甲状腺癌的去分化、进展和转移有关。TP53 R248的鉴定与该肿瘤的侵袭性临床行为相关。TSH受体功能获得性突变可以过度刺激甲状腺滤泡细胞，就像TSH水平升高一样，并可能有助于该肿瘤透明细胞形态的发展。这份报告是第一例甲状腺透明细胞滤泡癌的NGS分析，需要更多的分子特征来阐明发病机制，并提供更多的相关信息，这种罕见的甲状腺癌的变异。
Clear cell follicular carcinoma is a rare type of thyroid cancer and some with aggressive biological behavior. The cytoplasmic clearing of the neoplastic cells has been attributed to the accumulation of various substances, such as glycogen, lipid, mucin, and thyroglobulin, or distension of mitochondria or endoplasmic reticulum. However, the molecular mechanisms responsible for the characteristic appearance of the cell cytoplasm and the biological behavior remain unknown. We report here a case of aggressive clear cell follicular carcinoma of the thyroid with molecular profile using targeted next generation sequencing (NGS) that presented as a metastatic tumor in a woman with a history of breast carcinoma. The NGS data revealed the coexisting of a well-characterized loss-of-functionTP53 R248Qmutation and a putative gain-of-function mutation ofTSHR L272V, which was suggested by the overexpression of thyroglobulin andSLC5A5(NIS) genes in this tumor.TP53mutations are usually related with dedifferentiation, progression, and metastasis of thyroid carcinomas. Identification ofTP53 R248Qin this tumor correlated with its aggressive clinical behavior. Gain-of-function mutation ofTSHRcan overstimulate the thyroid follicular cells as the elevated level of TSH does and might have contributed to the development of clear cell morphology in this tumor. This report represents the first case of clear cell follicular carcinoma of the thyroid with NGS analysis and more molecular characterization is needed to elucidate the pathogenesis and provide more prognosis-relevant information for this uncommon variant of thyroid carcinomas.