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甲状腺癌是内分泌系统最常见的恶性肿瘤,其发病率在各个国家有逐年上升的趋势。起源于滤泡上皮细胞的甲状腺乳头状癌(papillary thyroid carcinoma,PTC)占甲状腺癌的80%~90%,是甲状腺癌最常见的病理类型,易较早发生颈部淋巴结的转移。PTC患者术后接受131I治疗残余甲状腺或转移灶,预后较好。
B型RAF基因(BRAF)是RAF(一种原癌基因,编码丝氨酸-苏氨酸蛋白激酶)基因家族的成员,位于人染色体7q34,含18个外显子,编码的蛋白质含783个氨基酸残基,相对分子质量约为94×103,属于丝氨酸-苏氨酸蛋白激酶类。约95%的BRAF基因突变都发生在第15号外显子的1799位核苷酸上,导致编码蛋白质的第600位密码子对应的缬氨酸被谷氨酸替代(V600E),即BRAFV600E突变,其他位点的突变比较少见。BRAFV600E突变是PTC中最常见的一种基因突变形式。BRAFV600E突变引起丝裂原活化的蛋白激酶通路的激活和持续活化,导致细胞无限分裂和肿瘤生成。
有文献报道,BRAFV600E基因的突变率在不同类型的PTC中不等,在经典型PTC中约为60%,高细胞型PTC中约为77%,滤泡变异性PTC中最低,约为12%;BRAFV600E突变只在PTC和比较明显的PTC来源的未分化甲状腺癌中有发现,而在滤泡状癌、髓样癌和良性甲状腺肿块(腺瘤和增生)中尚未发现[1]。研究表明,BRAFV600E突变与甲状腺外浸润和淋巴结转移相关[2-3]。Xing等[4]的研究显示,BRAFV600E突变与PTC的恶性程度存在很大的相关性。Lupi等[5]的大样本研究也支持了这一结论,他们还发现:BRAFV600E突变还与癌包膜的缺失存在很大关系,肿瘤缺少包膜则更容易发生转移和复发。BRAFV600E突变与PTC的发生、发展、预后等密切相关,其在临床中具有重要的应用价值。本文对BRAFV600E突变在PTC诊断、治疗和预后中的作用予以综述。
BRAFV600E基因突变在甲状腺癌中的临床应用研究进展
Advances in clinical utility of BRAFV600E mutation in thyroid cancer
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摘要: B型RAF基因(BRAF)编码蛋白质的第600位密码子对应的缬氨酸被谷氨酸替代(BRAFV600E突变)是甲状腺乳头状癌中最常见的基因突变。很多研究表明,该突变与甲状腺乳头状癌的发生、发展和转移密切相关。该文综合阐明BRAFV600E突变在甲状腺乳头状癌中的术前诊断、预后判断和抑制剂治疗等方面的临床应用,以便更好地指导临床决策。
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关键词:
- 原癌基因蛋白质B-raf /
- 甲状腺肿瘤 /
- 点突变 /
- 诊断
Abstract: Valine(V) being substituted for by glutamate(E)at codon 600 in B type RAF gene(BRAFV600E mutation)is the most common genetic mutation in papillary thyroid cancer. There have been many researches shown a strong association between BRAFV600E mutation and the occurrence, progression and metastasis of papillary thyroid cancer. This article illustrates its clinical utility on the preoperative diagnosis, prognosis evaluation and inhibitor treatment of papillary thyroid cancer, so as to instruct the clinical management better.-
Key words:
- Proto-oncogene protein B-raf /
- Thyroid neoplasms /
- Point mutation /
- Diagnosis
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