胃肠道命间质瘤.ppt

Click to edit title style ThemeGallery is a Design Digital Content Contents mall developed by Guild Design Inc. Contents Contents Contents Contents Diagram Describe a vision of company or strategic contents. Describe a vision of company or strategic contents. Describe a vision of company or strategic contents. Title in here Title in here Title in here ThemeGallery is a Design Digital Content Contents mall developed by Guild Design Inc. Diagram ThemeGallery is a Design Digital Content Contents mall developed by Guild Design Inc. A title about content Describe a vision of company or strategic contents. Diagram Please write down of contents explanation for Business Area. Business Area Business Area Business Area Business Area Please write down of contents explanation for Business Area. Please write down of contents explanation for Business Area. Please write down of contents explanation for Business Area. Please write down of contents explanation for Business Area. Diagram Title Title Title Description of the company’s products Description of the company’s technology Description of the company’s contents ThemeGallery is a Design Digital Content Contents mall developed by Guild Design Inc. Add your company slogan * * KIT的信号传导开始于ATP结合到距膜最近的KIT激酶区上，进而与将要被磷酸化的底物结合，随后磷酸基发生转移，被磷酸化的底物就有能力结合并激活下游的多种效应分子。 Savage DG, Antman KH. 伊马替尼–a new oral targeted therapy. N Engl J Med. 2002;346:683-693. Scheijen B, Griffin JD. Tyrosine kinase oncogenes in normal hematopoiesis and hematological disease. Oncogene. 2002;21:3314-3333. 超过 80%的GIST 具有 KIT 基因突变 外显子 11：发生在肥大细胞瘤和GIST中的细胞内近膜区 突变占所有GIST突变的近70% 通常是点突变（错义），装入缺失或重复 与构成性、非配体依赖的受体二聚化和激酶结构域激活相关联（获得性功能突变） 在高危GIST中发生频率高于中危GIST（不发生或很少发生在平滑肌瘤或平滑肌肉瘤中） 提示不良愈后：有突变的5年生存率为49%，而无外显子11突变的5年生存率为86% 外显子 9：发生在细胞近膜区的突变，有类似的激活机制 外显子 13：发生在分离的酪氨酸激酶结构域的突变也出现在GIST中 在其他疾病中鉴别出的其他 KIT 突变 外显子 17：磷酸转移酶结构域的突变发生在肥大细胞和生殖细胞中，导致无需二聚化的酪氨酸激酶的活化。外显子 17 突变使得肿瘤对伊马替尼耐药。 外显子 2：在2种血液疾病中鉴别出细胞外距膜最近的结构域发生的突变，这2种疾病是骨髓纤维变性和慢性粒细胞白血病。 7%的 GIST患者具有 PDGFRA 获得性功能基因内突变。 Tani