Tate Genshu, Suzuki Takao, Endo Yutaka, Mitsuya Toshiyuki
Department of Surgical Pathology, Showa University Fujigaoka Hospital, Fujigaoka 1-30, Aoba-ku, Yokohama 227-8501, Japan.
Cancer Genet Cytogenet. 2008 Jul;184(1):67-71. doi: 10.1016/j.cancergencyto.2008.03.013.
Cowden syndrome (CS), also known as multiple hamartoma syndrome, is an autosomal dominant cancer syndrome associated with a high risk of breast and thyroid cancers. The phosphatase and tensin homolog gene (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). PTEN inhibits angiogenesis, and germline mutations of the PTEN gene are associated with CS. We screened for mutations in the PTEN gene in two unrelated Japanese patients with CS. In one patient, who suffered from bilateral breast cancer, thyroid adenoma, and gastric malignant lymphoma, we found a single-base substitution in exon 2 (115G>C) of the PTEN gene. This transversion results in a germline missense mutation (A39P). To date, nine different mutations have been identified in exon 2 of the PTEN gene in patients with CS and variant CS; however, the A39P missense mutation has not been reported previously. We also detected a previously reported nonsense mutation, 697C>T, resulting in R233X.
考登综合征（CS），也称为多发性错构瘤综合征，是一种常染色体显性癌症综合征，与乳腺癌和甲状腺癌的高风险相关。磷酸酶和张力蛋白同源基因（PTEN）编码一种脂质磷酸酶，该酶含有一个蛋白酪氨酸磷酸酶结构域和一个C2结构域，并作为一种肿瘤抑制因子发挥作用，对由磷脂酰肌醇3-激酶（PI3K）启动的细胞存活信号通路起负调控作用。PTEN抑制血管生成，PTEN基因的种系突变与考登综合征相关。我们在两名无血缘关系的日本考登综合征患者中筛查了PTEN基因的突变。在一名患有双侧乳腺癌、甲状腺腺瘤和胃恶性淋巴瘤的患者中，我们在PTEN基因的外显子2（115G>C）中发现了一个单碱基替换。这种颠换导致了一个种系错义突变（A39P）。迄今为止，在考登综合征患者和变异型考登综合征患者的PTEN基因外显子2中已鉴定出九种不同的突变；然而，A39P错义突变此前尚未见报道。我们还检测到一个先前报道的无义突变，697C>T，导致R233X。
