High prevalence of BRAF mutations in thyroid cancer: genetic evidence for constitutive activation of the RET/PTC-RAS-BRAF signaling pathway in papillary thyroid carcinoma.
High prevalence of BRAF mutations in thyroid cancer: genetic evidence for constitutive activation of the RET/PTC-RAS-BRAF signaling pathway in papillary thyroid carcinoma.
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发表时间：
2003-04
期刊：
影响因子：
11.2
通讯作者：
E. Kimura;M. Nikiforova;Zhaowen Zhu;J. Knauf;Y. Nikiforov;J. Fagin
中科院分区：
文献类型：
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作者：
E. Kimura;M. Nikiforova;Zhaowen Zhu;J. Knauf;Y. Nikiforov;J. Fagin
甲状腺乳头状癌（PTCs）与RET或TRK酪氨酸激酶受体编码基因以及RAS基因的激活突变有关。最近在大多数黑色素瘤和一小部分结直肠肿瘤中报道了BRAF的激活突变。在这里，我们发现BRAF的体细胞突变V599E是ptc中最常见的遗传变化（78例中有28例；35.8%）。BRAF（V599E）突变是ptc所特有的，在任何其他类型的分化滤泡性肿瘤中均未发现（0 / 46）。此外，PTC与RET/PTC、BRAF或RAS突变之间没有重叠，这些突变总共存在于66%的病例中。这些突变缺乏一致性极不可能是偶然发生的。由于这些信号蛋白在甲状腺细胞中沿相同的途径起作用，这代表了一种独特的人类肿瘤发生模式，即通过三种信号效应器的串联突变。
Thyroid papillary cancers (PTCs) are associated with activating mutations of genes coding for RET or TRK tyrosine kinase receptors, as well as of RAS genes. Activating mutations of BRAF were reported recently in most melanomas and a small proportion of colorectal tumors. Here we show that a somatic mutation of BRAF, V599E, is the most common genetic change in PTCs (28 of 78; 35.8%). BRAF(V599E) mutations were unique to PTCs, and not found in any of the other types of differentiated follicular neoplasms arising from the same cell type (0 of 46). Moreover, there was no overlap between PTC with RET/PTC, BRAF, or RAS mutations, which altogether were present in 66% of cases. The lack of concordance for these mutations was highly unlikely to be a chance occurrence. Because these signaling proteins function along the same pathway in thyroid cells, this represents a unique paradigm of human tumorigenesis through mutation of three signaling effectors lying in tandem.