Genetic analyses for DNA replication error, beta-catenin gene, SKT11 etc.among the patients with gynecologic cancer

最近的研究表明，23%的子宫内膜癌和3%的卵巢癌存在RER异常，这些基因变化仅在子宫内膜样癌中检测到。RER阳性的子宫内膜癌患者预后较差，其中检出1例MMR基因突变(hMLH1等)。61例卵巢癌患者中有5例(8%)和35例子宫内膜癌患者中有5例(14%)检测到β-catenin基因突变，1例盆腔淋巴结微转移患者的β-catenin基因突变可能有助于淋巴结转移的分子诊断。推测SKT11基因是Peutz-Jegher综合征的致病基因。应用SSCP-Sequence方法对30例卵巢癌患者的STK11基因进行突变分析。仅1例在第6外显子出现CCG-CTG突变(Pro281-Leu)，2例在第5外显子出现额外条带。新的抗癌药物紫杉醇(紫杉醇)已被引入治疗卵巢癌。然而，在治疗卵巢癌之前，不能确定这些药物的化疗敏感性。我们试图通过基因改变，如P53、Bax、Bcl2等，寻找早期检测化疗药物敏感性的可能性，并分析耐药机制。结果表明，紫杉醇诱导的卵巢癌细胞凋亡通过两种不同的信号转导途径发挥重要作用，即P53非依赖途径和应激诱导途径，阻断这些途径和BAG-1或HSP70的过度表达可能是紫杉醇获得性耐药的重要因素。

The recent studies showed that the RER abnormalities were detected in 23 % for endometrial cancer and 3 % of ovarian cancer, which genetic changes were detected in only endometrioid type of cancer. The prognosis of RER positive patients (pts) with endometrial caner tended to be worse and among them a case with MMR gene mutation (hMLH1 etc) was detected.The mutation of beta-catenin gene were detected in 5 cases (8 %) of 61 ovarian cancer pts and 5 cases (14 %) of 35 endometrial cancer pts, and a micro metastasis of pelvic lymph node had a mutaton of beta-catenin gene,which might be useful for molecular diagnosis of lymph node metastasis.The putative SKT11 gene, which function is Serine/Threonine Kinase, was reported as causative gene of Peutz-Jegher Syndrome. We performed the mutational analysis of STK11 gene in 30 ovarian cancer pts by SSCP-Sequence method. Only one case showed its mutation of CCG-CTG(Pro281-Leu)at exon 6 and two cases showed extra bands at exon 5.A new anticancer drug group, Taxanes (Paclitaxel or Decetaxel) has been introduced for the treatment of ovarian cancer. However, chemosensitivities of these drugs are not determined before treatment of ovarian cancer. We tried to find out the possibilities of early detection of chemosensitivity by using genetic alteration, such as p53, BAX, Bcl-2 etc, and to analyze the mechanism of drug resistance. We showed that Paclitaxel-induced apoptosis played important roles of two different signal transductions, such as p53 independent pathway and stress-induced pathway in ovarian cancer cell lines, Blocking of these pathways and overexpression of bag-1 or hsp70 might be essential for the acquired resistance for Paclitaxel.