BRAFV599E mutation is the leading genetic event in adult sporadic papillary thyroid carcinomas
BRAFV599E mutation is the leading genetic event in adult sporadic papillary thyroid carcinomas
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DOI：
10.1210/jc.2003-031425
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发表时间：
2004-05-01
影响因子：
5.8
通讯作者：
Santeusanio, F
中科院分区：
文献类型：
--
作者：
Puxeddu, E;Moretti, S;Santeusanio, F
BRAF 的激活突变已在多种人类癌症中被发现，尤其是黑色素瘤和甲状腺乳头状癌 (PTC)。本研究的目的是揭示BRAF突变在甲状腺癌发展中的作用。研究了72个甲状腺肿瘤，包括60个PTC、6个滤泡性腺瘤、5个滤泡性癌和1个未分化癌。通过单链构象多态性和序列分析，BRAF突变筛查重点针对该基因的外显子15和外显子11。采用RT-PCR技术对RET/PTC表达进行搜索。BRAF基因的分子遗传学研究显示，60个PTC中的24个（40%）中，BRAF基因的第1796位核苷酸存在胸腺嘧啶到腺嘌呤的错义颠倒，导致V599E取代，6个滤泡性腺瘤中没有一个，5个滤泡性癌中没有一个，1个间变性癌中没有一个。此外，60 个 PTC 中有 9 个（15%）呈现 RET/PTC 表达。遗传临床关联分析显示，BRAF 突变与经典乳头状组织型 PTC 的发育之间存在统计学显着相关性 (P = 0.038)。相反，在 BRAF (V599E) 的表达与诊断时的年龄、性别、尺寸和原发性癌症的局部侵袭性、淋巴结转移的存在、肿瘤分期和疾病的多灶性之间没有检测到任何联系。这些数据清楚地证实，BRAF (V599E) 是迄今为止在成人散发性 PTC 中发现的更常见的基因改变，它对于这种甲状腺癌组织型来说是独特的，并且可能推动甲状腺癌的发展。经典乳头状亚型的 PTC。
Activating mutations of BRAF have been identified in a variety of human cancers, most notably melanomas and papillary thyroid carcinomas (PTCs). The aim of the present study was to disclose the role of BRAF mutations in thyroid carcinoma development.Seventy-two thyroid tumors, including 60 PTCs, six follicular adenomas, five follicular carcinomas, and one anaplastic carcinoma, were studied. BRAF mutation screening focused on exon 15 and exon 11 of the gene by single-stranded conformational polymorphism and sequence analysis. Search of RET/PTC expression was conducted with the RT-PCR technique.The molecular genetic study of the BRAF gene showed the presence of a missense thymine to adenine transversion at nucleotide 1796, resulting in the V599E substitution, in 24 of 60 PTCs (40%), none of six follicular adenomas, and none of five follicular carcinomas or one anaplastic carcinoma. Moreover, nine of 60 PTCs (15%) presented RET/PTC expression. A genetico-clinical association analysis showed a statistically significant correlation between BRAF mutation and development of PTCs of the classic papillary histotype ( P = 0.038). On the contrary, no link could be detected between expression of BRAF(V599E) and age at diagnosis, gender, dimension, and local invasiveness of the primary cancer, presence of lymph node metastases, tumor stage, and multifocality of the disease.These data clearly confirm that BRAF(V599E) is the more common genetic alteration found to date in adult sporadic PTCs, that it is unique for this thyroid cancer histotype, and that it might drive the development of PTCs of the classic papillary subtype.