BRAF mutations in thyroid tumors are restricted to papillary carcinomas and anaplastic or poorly differentiated carcinomas arising from papillary carcinomas
BRAF mutations in thyroid tumors are restricted to papillary carcinomas and anaplastic or poorly differentiated carcinomas arising from papillary carcinomas
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DOI：
10.1210/jc.2003-030838
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发表时间：
2003-11-01
影响因子：
5.8
通讯作者：
Nikiforov, YE
中科院分区：
文献类型：
--
作者：
Nikiforova, MN;Kimura, ET;Nikiforov, YE
BRAF基因的激活点突变最近在甲状腺乳头状癌中有报道。在这项研究中，我们分析了320个甲状腺肿瘤和6个未分化癌细胞系，并在45个（38%）乳头状癌、2个（13%）低分化癌、3个（10%）未分化癌和5个（83%）甲状腺未分化癌细胞系中检测到BRAF突变，但在滤泡癌、Hurthle细胞癌和髓样癌、滤泡腺瘤和Hurthle细胞腺瘤中未检测到BRAF突变。或良性增生结节。所有突变均涉及核苷酸1796处的T->A颠换。在乳头状癌中，BRAF突变与年龄较大、经典乳头状癌或高细胞变异组织学、甲状腺外延伸以及III期和IV期更频繁的表现相关。所有BRAF阳性的低分化和间变性癌都含有预先存在的乳头状癌区域，并且在高分化和去分化成分中都存在突变。这些数据表明BRAF突变仅限于乳头状癌和乳头状癌引起的低分化和间变性癌。它们与乳头状癌的不同表型和生物学特性相关，并可能参与向低分化癌和间变性癌的进展。
Activating point mutations of the BRAF gene have been recently reported in papillary thyroid carcinomas. In this study, we analyzed 320 thyroid tumors and six anaplastic carcinoma cell lines and detected BRAF mutations in 45 (38%) papillary carcinomas, two (13%) poorly-differentiated carcinomas, three (10%) anaplastic carcinomas, and five (83%) thyroid anaplastic carcinoma cell lines but not in follicular, Hurthle cell, and medullary carcinomas, follicular and Hurthle cell adenomas, or benign hyperplastic nodules. All mutations involved a T-->A transversion at nucleotide 1796. In papillary carcinomas, BRAF mutations were associated with older age, classic papillary carcinoma or tall cell variant histology, extrathyroidal extension, and more frequent presentation at stages III and IV. All BRAF-positive poorly differentiated and anaplastic carcinomas contained areas of preexisting papillary carcinoma, and mutation was present in both the well-differentiated and dedifferentiated components. These data indicate that BRAF mutations are restricted to papillary carcinomas and poorly differentiated and anaplastic carcinomas arising from papillary carcinomas. They are associated with distinct phenotypical and biological properties of papillary carcinomas and may participate in progression to poorly differentiated and anaplastic carcinomas.