Tate Genshu, Suzuki Takao, Nemoto Hiroshi, Kishimoto Koji, Hibi Kenji, Mitsuya Toshiyuki
Department of Pathology, Showa University Fujigaoka Hospital, Fujigaoka 1-30, Aoba-ku, Yokohama 227-8501, Japan.
Cancer Genet Cytogenet. 2009 Sep;193(2):104-8. doi: 10.1016/j.cancergencyto.2009.04.005.
A tumor suppressor gene at 10q23.3, designated PTEN, encoding a dual-specificity phosphatase with lipid and protein phosphatase activity, has been shown to play an essential role in the pathogenesis of a variety of human cancers. Frequent mutations and deletions of PTEN genes are found in cancer. Little is known, however, about the role that PTEN plays in the pathogenesis of a primary choriocarcinoma derived from gastric adenocarcinoma, an extremely rare choriocarcinoma, or in extragonadal retroperitoneal choriocarcinoma. In this study, genetic alterations occurring in extragonadal choriocarcinoma in two Japanese male patients were examined. Loss of heterozygosity (LOH) analysis using a polymorphic marker of the PTEN gene, IVS4+109ins/delTCTTA, revealed a hemizygous deletion of PTEN not only in the primary gastric choriocarcinoma, but also in the gastric adenocarcinoma. Microsatellite marker D12S1051 likewise showed LOH in both the primary gastric choriocarcinoma and the gastric adenocarcinoma. Mutational analysis of the TP53 gene revealed a point mutation in exon 5 (A536G), which resulted in H179R in the gastric choriocarcinoma but not in the gastric adenocarcinoma. No LOH was found for PTEN in an extragonadal retroperitoneal choriocarcinoma. Microsatellite marker D9S162 showed LOH in the extragonadal retroperitoneal choriocarcinoma, but not in the primary gastric choriocarcinoma. These results indicate that LOH of the PTEN gene and of D12S1051 is the molecular pathogenesis of the gastric adenocarcinoma, and the mutation of the TP53 gene is an additional hit for the oncogenesis of choriocarcinoma arising from gastric adenocarcinoma. However, LOH of the PTEN gene is not a common molecular event for pathogenesis of extragonadal choriocarcinoma. In addition, it was found that expression of PTEN is significantly decreased in the nuclei of syncytiotrophoblast-like cancer cells, compared with those of cytotrophoblast-like cancer cells in choriocarcinoma.
位于10q23.3的一种肿瘤抑制基因，命名为PTEN，编码一种具有脂质和蛋白质磷酸酶活性的双特异性磷酸酶，已被证明在多种人类癌症的发病机制中起重要作用。在癌症中发现PTEN基因频繁发生突变和缺失。然而，对于PTEN在源自胃腺癌（一种极其罕见的绒毛膜癌）的原发性绒毛膜癌或性腺外腹膜后绒毛膜癌发病机制中的作用知之甚少。在本研究中，对两名日本男性患者性腺外绒毛膜癌中发生的基因改变进行了检测。使用PTEN基因的多态性标记IVS4 + 109ins/delTCTTA进行杂合性缺失（LOH）分析，结果显示不仅原发性胃绒毛膜癌，而且胃腺癌中均存在PTEN的半合子缺失。微卫星标记D12S1051同样在原发性胃绒毛膜癌和胃腺癌中均显示出LOH。TP53基因的突变分析显示外显子5存在点突变（A536G），该突变在胃绒毛膜癌中导致H179R，但在胃腺癌中未出现。在性腺外腹膜后绒毛膜癌中未发现PTEN的LOH。微卫星标记D9S162在性腺外腹膜后绒毛膜癌中显示出LOH，但在原发性胃绒毛膜癌中未显示。这些结果表明，PTEN基因和D12S1051的LOH是胃腺癌的分子发病机制，而TP53基因的突变是胃腺癌来源的绒毛膜癌发生肿瘤的另一个因素。然而，PTEN基因的LOH并非性腺外绒毛膜癌发病机制中的常见分子事件。此外，还发现与绒毛膜癌中细胞滋养层样癌细胞相比，合体滋养层样癌细胞核中PTEN的表达明显降低。
