卵巢癌组织17号染色体位点的微卫星不稳定性的研究

Microsatellite instability of ovarian cancer tissue in chromosome 17

目的探讨卵巢癌组织微卫星不稳定性 (Microsatellite Instability,MIN)的表现。方法在 2 3例卵巢癌新鲜组织和自身癌旁正常组织的 DNA中 ,用聚合酶链反应 (PCR)扩增 17号染色体上 5个微卫星位点 ,用单链构象多态性 (Single Strand Conform ation Polymorphism,SSCP)分析法检测微卫星不稳定性 (MIN) ,并用银染方法显示结果。结果在 2 3例卵巢癌组织中均有不同程度的 MIN发生 ,其中浆液性卵巢癌阳性率明显高于其他类型卵巢癌 ; ～ 期肿瘤微卫星不稳定性高于 ～ 期肿瘤。在 17号染色体长臂上的 3个微卫星位点 D17S85 5、D17S80 6和 D17S5 79的 MIN的发生率分别为 4/ 2 3、7/ 2 3、6 / 2 3,短臂上 2个位点 D17S5 13和 TP5 3的 MIN的发生率分别为 2 / 2 3和 4/ 2 3,长臂的阳性率明显高于短臂 ,表明长臂比短臂更不稳定。有 4例病例在短臂和长臂处均出现 MIN,表明 17号染色体的长臂和短臂出现 MIN是卵巢癌普遍发生的现象。结论 17号染色体定位于 BRCA1附近的 3个微卫星位点以及 p5 3附近的微卫星位点均频繁地出现 MIN。证实了频繁发生微卫星不稳定的染色体区域附近 ,可能存在抑癌基因 ,并且有可能引起抑癌基因功能的丧失。位于端粒处的 D17S5 13发生 MIN,可以推测在端粒至 p5

Objective Examination of the frequency of microsatellite instability (MIN) on chromosome 17 in 23 sporadic ovarian tumors. Methods We examined the frequencies of MIN at five different loci on chromosome 17 in 23 epithelial ovarian tumors by polymerase chain reaction (PCR)based single strand conformation polymorphism (PCR SSCP). Results MIN on 17p and 17q was observed to be 4/23 and 7/23, respectively. MIN at D17D513 was detected in 2/23 of malignant cases and in 4/23 at TP53. The marker D17S855, D17S806 and D17S579 at or close to the BRCA1 gene showed MIN in 4/23, 7/23, 6/23 cases respectively. The data presented here suggested that loss of the whole chromosome 17 is a relatively frequent event in ovarian carcinomas and 17q is more unstable than 17p. Conclusion MIN on 17p at or close to the p53 locus and on 17q at or close to the breast and ovarian cancer susceptibility BRCA1 is present very frequently in ovarian cancers. MIN at D17S513 may imply the presence of a tumor suppressor gene at the region telomeric to p53. High incidence of MIN was observed in serious ovarian carcinomas than other histological subtypes and was associated with advanced stages and poor outcome.