Clinical implication of hot spot BRAF mutation, V599E, in papillary thyroid cancers
Clinical implication of hot spot BRAF mutation, V599E, in papillary thyroid cancers
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DOI：
10.1210/jc.2003-030305
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发表时间：
2003-09-01
影响因子：
5.8
通讯作者：
Yamashita, S
中科院分区：
文献类型：
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作者：
Namba, H;Nakashima, M;Yamashita, S
最近在人类癌症中报道了BRAF激酶基因的激活突变。本研究的目的是确定甲状腺癌中BRAF突变的频率及其与临床病理参数的相关性。我们分析了6个人甲状腺癌细胞系和207例石蜡包埋甲状腺肿瘤组织中BRAF基因的第11和15外显子。在6个细胞系中的4个和207个甲状腺肿瘤中的51个（24.6%; 20个滤泡性腺瘤中的0个，11个滤泡性癌中的0个，170个乳头状癌中的49个，和6个未分化癌中的2个）中发现了外显子15的T1796 A（V599 E）错义突变。在BRAF突变的细胞系中观察到MAPK激酶-MAPK通路的激活。BRAF突变相关的增强细胞生长被MAPK激酶抑制剂U 0126抑制。对126例甲状腺乳头状癌患者的检测结果显示，BRAF突变与远处转移（P=0.033）和临床分期（P=0.049）显著相关。我们的研究结果表明，BRAF基因的激活突变可能是一个潜在的有用的标志物，晚期甲状腺癌患者的预后。
Activating mutations in the BRAF kinase gene have recently been reported in human cancers. The aim of the present study was to determine the frequency of BRAF mutations in thyroid cancer and their correlation with clinicopathological parameters. We analyzed exons 11 and 15 of BRAF gene in six human thyroid cancer cell lines and 207 paraffin-embedded thyroid tumor tissues. A missense mutation was found at T1796A (V599E) in exon 15 in four of the six cell lines and 51 of 207 thyroid tumors (24.6%; 0 of 20 follicular adenoma, 0 of 11 follicular carcinoma, 49 of 170 papillary carcinomas, and 2 of 6 undifferentiated carcinomas). Activation of MAPK kinase-MAPK pathway was observed in cell lines harboring BRAF mutation. BRAF mutation-associated enhanced cell growth was suppressed by MAPK kinase inhibitor, U0126. Examination of 126 patients with papillary thyroid cancer showed that BRAF mutation correlated significantly with distant metastasis (P=0.033) and clinical stage (P=0.049). Our results indicate that activating mutation of BRAF gene could be a potentially useful marker of prognosis of patients with advanced thyroid cancers.