Kitamura Yukihiko, Hirota Seiichi, Nishida Toshirou
Department of Pathology, Medical School/Graduate School of Frontier Biosicence, Osaka University, Suita, Osaka 565-0871, Japan.
Cancer Sci. 2003 Apr;94(4):315-20. doi: 10.1111/j.1349-7006.2003.tb01439.x.
Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the human gastrointestinal (GI) tract. The c-kit receptor tyrosine kinase (KIT) is expressed by practically all GISTs, and gain-of-function mutations of KIT are present in most GISTs. Interstitial cells of Cajal (ICC) are the pacemaker of the peristaltic movement of the GI tract. Since signals through KIT are essential for development of ICC and since multiple GISTs develop from the hyperplastic lesion of ICCs in familial GIST patients with germline mutations of KIT, GISTs are considered to originate from ICC. Imatinib mesylate, which was developed for treatment of chronic myeloid leukemia (CML), was found to be useful for treatment of GISTs. Imatinib mesylate inhibits BCR-ABL fused tyrosine kinase that causes CML. Imatinib mesylate also inhibits the mutated KIT observed in most GISTs, and this explains the effectiveness of Imatinib mesylate on GISTs. GISTs appear to serve as a model for molecule-based diagnosis and treatment of solid tumors.
胃肠道间质瘤（GIST）是人类胃肠道最常见的间充质肿瘤。几乎所有的GIST都表达c-kit受体酪氨酸激酶（KIT），并且大多数GIST中都存在KIT功能获得性突变。 Cajal间质细胞（ICC）是胃肠道蠕动运动的起搏器。由于通过KIT的信号对于ICC的发育至关重要，并且由于在具有KIT种系突变的家族性GIST患者中，多个GIST从ICC的增生性病变发展而来，因此GIST被认为起源于ICC。发现用于治疗慢性粒细胞白血病（CML）的甲磺酸伊马替尼对治疗GIST有用。甲磺酸伊马替尼抑制引起CML的BCR-ABL融合酪氨酸激酶。甲磺酸伊马替尼还抑制大多数GIST中观察到的突变KIT，这解释了甲磺酸伊马替尼对GIST的有效性。GIST似乎可作为实体瘤基于分子的诊断和治疗的模型。
