Thyroid cancer study for establishment of prognostic marker and molecular targeting therapy using gene mutation analysis.

甲状腺乳头状癌中BRAF基因突变率高，主要局限于外显子15密码子600（BRAF^<V600E>）。BRAF是RAF激酶蛋白家族中位于RAS下游的蛋白质之一。BRAF是一种丝氨酸/苏氨酸激酶，作为细胞内信号传递因子作用于MEK 1/2<V600E>。它识别约30 - 60%的成人甲状腺乳头状癌。详细的组织病理学分析显示，BRAF^<V600E>突变在经典乳头型和高细胞变异型中频率高，但在滤泡变异型中频率低。提示BRAF基因突变与成年期甲状腺上皮细胞乳头状变密切相关。我们的研究提出术前通过BRAF基因分析，利用BRAF突变对成人甲状腺乳头状癌的特异性来确诊。此外，我们还报道了儿童甲状腺乳头状癌中BRAF突变的低频率。我们还报道了紫杉醇和NF-κ B抑制剂DHMEQ作为一种新的分子靶向治疗药物对甲状腺未分化癌的良好疗效。

High prevalence of mutations in BRAF gene which mostly restricted in exon 15 codon 600 (BRAF^<V600E>) was found in thyroid papillary carcinomas. BRAF is one of the RAF kinase protein family proteins that were located downstream of RAS. BRAF is a serine/threonine kinase and operates as intracellar signal transfer factor to MEK1/2.BRAF^<V600E> is detected in the different frequency between adult and childhood thyroid carcinomas. It is recognizes about 30 to 60 % of adult papillary thyroid carcinomas. Detailed histopathological analysis have revealed high frequency of BRAF^<V600E> mutation in classical papillary type and tall cell variant type, but low frequency in follicular variant type. These findings suggest that BRAF mutation is closely related with papillary transforming of thyroid epithelial cells in adulthood. Our study puts forward that pre-operative BRAF gene analysis to confirm the diagnosis through the use of specificity of BRAF mutation to adult papillary thyroid carcinoma. Furthermore, we have reported low frequency of BRAF mutation among childhood papillary thyroid carcinomas. We.also reported the good effects of taxsol and NF-kB inhibitor, DHMEQ to anaplastic thyroid cancer as a new molecular targeting therapeutic drugs.