Department of Pathology, University of Toronto, Toronto, ON, Canada.
Endocr Pathol. 2010 Dec;21(4):250-2. doi: 10.1007/s12022-010-9129-4.
Activating mutations of GNAq protein in a hotspot at codon 209 have been recently described in uveal melanomas. Since these neoplasms share with thyroid carcinomas a high frequency of MAP kinase pathway-activating mutations, we hypothesized whether GNAq mutations could also play a role in the development of thyroid carcinomas. Additionally, activating mutations of another subtype of G protein (GNAS1) are frequently found in hyperfunctioning thyroid adenomas, making it plausible that GNAq-activating mutations could also be found in some of these nodules. To investigate thyroid papillary carcinomas and thyroid hyperfunctioning nodules for GNAq mutations in exon 5, codon 209, a total of 32 RET/PTC, BRAF, and RAS negative thyroid papillary carcinomas and 13 hyperfunctioning thyroid nodules were evaluated. No mutations were identified. Although plausible, GNAq mutations seem not to play an important role in the development of thyroid follicular neoplasms, either benign hyperfunctioning nodules or malignant papillary carcinomas. Our results are in accordance with the literature, in which no GNAq hotspot mutations were found in thyroid papillary carcinomas, as well as in an extensive panel of other tumors. The molecular basis for MAP-kinase pathway activation in RET-PTC/BRAF/RAS negative thyroid carcinomas remains to be determined.
在葡萄膜黑色素瘤中，最近描述了 GNAq 蛋白在密码子 209 的热点处的激活突变。由于这些肿瘤与甲状腺癌一样，具有高频的 MAP 激酶通路激活突变，我们假设 GNAq 突变是否也可能在甲状腺癌的发展中发挥作用。此外，另一种 G 蛋白亚型（GNAS1）的激活突变经常在功能亢进的甲状腺腺瘤中发现，这使得 GNAq 激活突变也可能存在于其中一些结节中。为了研究甲状腺乳头状癌和甲状腺功能亢进结节中 GNAq 外显子 5 密码子 209 的突变，共评估了 32 例 RET/PTC、BRAF 和 RAS 阴性甲状腺乳头状癌和 13 例功能亢进性甲状腺结节。未发现突变。虽然合理，但 GNAq 突变似乎在甲状腺滤泡性肿瘤的发展中，无论是良性功能亢进结节还是恶性乳头状癌中，都不起重要作用。我们的结果与文献一致，即甲状腺乳头状癌以及其他广泛的肿瘤中均未发现 GNAq 热点突变。RET-PTC/BRAF/RAS 阴性甲状腺癌中 MAP 激酶通路激活的分子基础仍有待确定。
