Tate Genshu, Suzuki Takao, Mitsuya Toshiyuki
Department of Surgical Pathology, Showa University Fujigaoka Hospital, Fujigaoka 1-30, Yokohama, Japan.
Cancer Genet Cytogenet. 2007 Oct 15;178(2):160-2. doi: 10.1016/j.cancergencyto.2007.07.017.
The phosphatase and tensin homolog (mutated in multiple advanced cancers 1) gene, or PTEN, encodes a lipid phosphatase that contains a PTPase domain and a C2 domain and plays a role as a tumor suppressor that negatively regulates the cell-survival signaling pathway initiated by phosphatidylinositol 3-kinase (PI3K). The PTEN protein inhibits angiogenesis, and somatic mutations of the PTEN gene are involved in canine hemangiosarcoma. We screened for mutations of the PTEN gene in two patients with human hepatic angiosarcoma to determine whether PTEN is involved in the pathogenesis of human hepatic angiosarcoma. In one patient, who suffered from breast cancer, pharyngeal cancer, and hepatic angiosarcoma, we found a single base substitution in exon 7 (640C>T) of the PTEN gene in both the hepatic angiosarcoma and normal tissues. This transition results in a germline nonsense mutation (Q214X). These findings indicate that analysis of PTEN gene mutations may be useful for characterization of the molecular event in hepatic angiosarcoma and cancer predisposition.
磷酸酶与张力蛋白同源物（在多种晚期癌症中发生突变 1）基因，即 PTEN，编码一种脂质磷酸酶，该酶含有一个蛋白酪氨酸磷酸酶（PTPase）结构域和一个 C2 结构域，并作为肿瘤抑制因子发挥作用，负向调节由磷脂酰肌醇 3 - 激酶（PI3K）启动的细胞存活信号通路。PTEN 蛋白抑制血管生成，并且 PTEN 基因的体细胞突变与犬血管肉瘤有关。我们筛查了两名人类肝血管肉瘤患者的 PTEN 基因突变，以确定 PTEN 是否参与人类肝血管肉瘤的发病机制。在一名患有乳腺癌、咽癌和肝血管肉瘤的患者中，我们在肝血管肉瘤组织和正常组织中均发现 PTEN 基因第 7 外显子存在单碱基替换（640C>T）。这种转换导致了一个种系无义突变（Q214X）。这些发现表明，PTEN 基因突变分析可能有助于表征肝血管肉瘤中的分子事件以及癌症易感性。
