文档介绍：李永平 Doctor Li BRAF 基因突变在甲状腺乳头状癌中的临床应用 201 4- 04 - 23 *目录 CONTENTS 相关文献回顾 BRAF 基因 BRAF 与 PTC 文献精选展望*相关文献回顾 1 * BRAF 文献回顾 BRAF Mutations in Hairy- Cell Leukemia ? The BRAF V600E mutation was present in all patients with HCL who were evaluated ? Implications for the pathogenesis, diagnosis, and targeted therapy ? N Engl J Med June 16 2011;364:2305-15. ; 毛细胞白血病?所有毛细胞白血病 BRAF V600E 发生了变异?可以用来研究发病机理、诊断、靶向治疗* BRAF 文献回顾 Cetuximab and Chemotherapy as Initial Treatment for Metastatic Colorectal Cancer ? Cetuximab plus FOLFIRI compared with FOLFIRI alone reduced the risk of progression of metastatic colorectal cancerN ? Engl J Med april 2,2009;360:1408-17. 转移性结直肠癌?西妥昔单抗合并 FOLFIRI 降低对 KRAS 突变转移性结直肠癌患者的疾病进展风险? 2011 版提出:具有 BRAF 突变的患者预后差,一线治疗后疾病进展的,利用西妥昔单抗治疗是无效的* BRAF 文献回顾 Improved Survival With Vemurafenib In Melanoma With BRAF V600E Mutation ? Aberrant activation of the BRAF kinase occurs in 60% of melanomas, and although BRAF inhibitors have shown significant early clinical ess ? N Engl J Med 2011;364:2507-16. 黑色素瘤?在黑色素瘤中有 60% 患者发生 BRAF V600E 突变?发生 BRAF V600E 突变的患者经 vemurafenib (威罗菲尼)治疗, 患者的总生存率和无进展生存率分别提高( 37%&26% )。但易产生耐药。* BRAF 基因介绍 2 * PTC 中 BRAF 基因突变的分布 The worldwide prevalence of BRAF mutations in PTC Endocrine-Related Cancer (2006) 13 455 – 464 文献结论※ B-RAF V600E mutation was found in 99 out of 260 PTCs (38%) ※ The B-RAF V600E mutation was present in % of cases of classic PTC (85 out of 176), in % (nine out of 51) of follicular variants of PTC, in % (five out of 23) of other PTC variants and in none of the ten poorly differentiated tumors. ※ The B-RAF V600E was correlated with an older age at diagnosis (P = ) Endocrine-Related Cancer (2006) 13 455 – 464 BRAF 基因突变的致病机理 The model illustrates the two major signaling pathways, the PI3K/Akt and the MAP kinase pathways 。 The increasing color intensity of the circle represents the increasing progression and aggressivenes