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%的卵巢癌检测到RER异常，其中仅在子宫内膜样癌中检测到遗传改变。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%）检测到β -catenin基因突变，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中有β -catenin基因突变，可能对淋巴结转移的分子诊断有帮助。SKT11基因的功能是丝氨酸/苏氨酸激酶，被认为是Peutz-Jegher综合征的致病基因。采用SSCP-Sequence法对30例卵巢癌患者的STK11基因进行突变分析。CCG-CTG(Pro281-Leu) 6外显子突变1例，5外显子突变2例。一种新的抗癌药物，紫杉醇（紫杉醇或Decetaxel）已被引入治疗卵巢癌。然而，这些药物的化学敏感性在卵巢癌治疗前并不确定。我们试图通过基因改变，如p53、BAX、Bcl-2等，探索早期发现化疗敏感性的可能性，并分析耐药机制。我们发现紫杉醇诱导的细胞凋亡在卵巢癌细胞系中p53独立通路和应激诱导通路两种不同的信号转导中起重要作用，阻断这些通路和bag-1或hsp70的过表达可能是紫杉醇获得性耐药的必要条件。

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.