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机构地区:[1]中国医科大学附属第二临床学院妇产科,沈阳110004 [2]中国医科大学卫生部细胞生物学重点实验室 [3]中国医学科学院基础医学研究所遗传室
出 处:《中华肿瘤杂志》2005年第11期657-659,共3页Chinese Journal of Oncology
基 金:国家自然科学基金资助项目(30100104);国家重点基础研究发展规划项目(G1998051203);辽宁省博士启动基金资助课题(20021035)
摘 要:目的探讨RASSF1A基因启动子区异常甲基化与卵巢上皮性恶性肿瘤发生、发展的关系。方法应用甲基化特异性PCR方法,检测80例卵巢上皮性恶性肿瘤组织RASSF1A基因启动子区异常甲基化。结果80例卵巢上皮性恶性肿瘤组织中,RASSF1A基因启动子区甲基化的发生率为52.5%,而相应癌旁正常组织中,RASSF1A基因启动子区均未发生甲基化(P<0.05)。浆液性癌、黏液性癌和内膜样癌中,RASSF1A基因启动子区甲基化的发生率分别为54.2%、52.4%和45.5%,差异无统计学意义。临床Ⅰ期、Ⅱ期卵巢上皮性恶性肿瘤RASSF1A基因启动子区甲基化的发生率分别为21.4%和16.7%,明显低于临床Ⅲ期(66.7%)和Ⅳ期(77.8%)。高分化组和中分化组RASSF1A基因启动子区甲基化的发生率分别为34.5%和35.0%,均低于低分化组(80.6%)。结论卵巢上皮性恶性肿瘤组织中存在RASSF1A基因启动子区的异常甲基化,甲基化与卵巢上皮性恶性肿瘤的临床分期和组织学分级有关。Objective To investigate hypermethylation of promoter region of RASSF1A and its relationship with ovarian malignant epithelial tumors. Methods Methylation-specific PCR(MSP) was used to determine the hypermethylation of promoter region of ras association domain family 1 ( RASSF1A) gene in 80 cases of ovarian malignant epithelial tumors, Results No methylation of promoter region of RASSF1A gene was fnund in all 80 normal control tissues (0). Of 80 ovarian malignant epithelial tumors 42 were hypermethylated in promoter region of RASSF1A gene (52. 5% ). There was no statistically significant difference in the frequency of hypermethylation of RASSF1A gene among serious adenocarcinomas, mueinous adenocarcinomas and endometrioid adenocarcinomas (54. 2%, 52. 4% and 45. 5%, respectively; P 〉 0.05 ). Hypermethylation of RASSF1A gene happened more often in tumors in stage Ⅲ and Ⅳ (66.7% and 77.8% ) than that in stage Ⅰ and Ⅱ (21.4% and 16.7% ;P〈0.05). It was less frequently observed in well and moderately differentiated tumors ( 34. 5% and 35. 0% ) than in poorly differentiated tumors (80.6% ;P 〈0.05 ). Conclusion High frequency of methylation of RASSF1A promoter exists in ovarian malignant epithelial tumors As a tumor suppressor gene, its suppressor activity may be abrogated by an epigenetie mechanism. Hypermethylation of RASSF1A promoter in patients with epithelial malignant ovarian tumors is related to clinical stage and histopathological grade. It indicates poor prognosis.
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