Department of Hospital Pathology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Thyroid. 2012 Aug;22(8):791-7. doi: 10.1089/thy.2011.0123. Epub 2012 Apr 3.
BRAF mutation is the most common genetic event in papillary thyroid carcinoma (PTC); however, the prevalence and patterns of the mutation vary worldwide. We investigated the frequency and type of BRAF mutations based on the histologic subtypes in a large cohort of Korean patients with PTC.
A total of 1041 consecutive PTCs were classified according to histologic subtypes. BRAF mutations were examined by denaturing high-performance liquid chromatography and direct sequencing. Rare complex mutations were confirmed by molecular cloning of polymerase chain reaction amplicons and sequencing of the products.
BRAF mutations were found in 839 (80.6%) of 1041 patients with PTC. The histologic subtype-specific prevalence of BRAF mutation was as follows: 85.3% (249/292) were classic, 45.8% (11/24) were follicular, 79.9% (576/721) were microcarcinoma, and 75.0% (3/4) were other variants. In addition to the usual c.1799T>A mutation, we identified other four mutation types: c.[1795_1796insA;1770_1795dup26], c.[1742-10T>C;1799T>A] and c.[1796C>G;1799T>A], and c.1799_1800TG>AA, respectively. The former three were novel mutations in thyroid tumors. Within the series of microcarcinoma variants, the BRAF mutation rate was lower in tumors with follicular morphology than those with nonfollicular types (66.7% vs. 80.9%, p=0.0145).
Out of 1041 Korean patients with PTC, 0.4% had rare types of BRAF mutation and three new somatic mutations were identified. The BRAF mutation rate was quite low in PTC with follicular morphology regardless of tumor size. However, the prevalence of BRAF mutation in microcarcinoma and follicular variants of PTC is relatively high in Korea and its analysis may be clinically useful for managing the patients.
BRAF 突变是甲状腺乳头状癌（PTC）中最常见的遗传事件；然而，突变的流行率和模式在全球范围内有所不同。我们根据韩国大量 PTC 患者的组织学亚型，研究了 BRAF 突变的频率和类型。
共对 1041 例连续的 PTC 进行组织学亚型分类。通过变性高效液相色谱和直接测序检测 BRAF 突变。通过聚合酶链反应扩增子的分子克隆和产物测序证实罕见的复杂突变。
在 1041 例 PTC 患者中，发现 839 例（80.6%）存在 BRAF 突变。BRAF 突变的组织学亚型特异性患病率如下：经典型 85.3%（249/292），滤泡型 45.8%（11/24），微癌 79.9%（576/721），其他变异型 75.0%（3/4）。除了常见的 c.1799T>A 突变外，我们还鉴定了其他四种突变类型：c.[1795_1796insA;1770_1795dup26]、c.[1742-10T>C;1799T>A] 和 c.[1796C>G;1799T>A]，以及 c.1799_1800TG>AA。前三种是甲状腺肿瘤中的新突变。在微癌变异系列中，滤泡形态的肿瘤 BRAF 突变率低于非滤泡类型（66.7% vs. 80.9%，p=0.0145）。
在 1041 例韩国 PTC 患者中，0.4%存在罕见类型的 BRAF 突变，发现三种新的体细胞突变。无论肿瘤大小如何，滤泡形态的 PTC 的 BRAF 突变率都相当低。然而，韩国的 PTC 中 BRAF 突变在微癌和滤泡变异型中的发生率相对较高，其分析可能对管理患者具有临床意义。
