Lee J H, Kang Y S, Park S Y, Kim B G, Lee E D, Lee K H, Park K B, Kavanagh J J, Wharton J T
Department of Obstetrics and Gynecology, Korea Cancer Center Hospital, Seoul, Korea.
Cancer Genet Cytogenet. 1995 Nov;85(1):43-50. doi: 10.1016/0165-4608(95)00116-6.
We have investigated a series of 19 human ovarian carcinomas and 17 borderline ovarian tumors to determine the loss of heterozygosity on chromosome 17p and possible concurrent p53 mutations. Allelic losses were assessed using restriction fragment length polymorphism study, and p53 gene mutations were detected by single strand conformation polymorphism analysis and by direct sequencing. In addition, we stained the same tumor sections immunohistochemically to detect p53 protein in tissues. Among 19 ovarian malignant tumor samples tested, we identified 17p allelic deletions in 12 (63.2%) of 19 informative cases. The p53 gene mutation was observed in 7 of 19 (36.8%) malignant ovarian tumors, and it was predominantly observed in tumors with allelic loss on 17p (six of seven tumors, 85.7%). Although 9 cases of 17 borderline ovarian tumors showed shifted bands on single strand conformation polymorphism analysis, only one case was proved to have a point mutation in direct sequencing. We also obtained six cases (31.6%) of positive immunoreactivity from 19 ovarian cancers and 3 cases (17.6%) from 17 borderline ovarian tumors. We conclude that loss or inactivation of tumor suppressor gene function by chromosome 17p allelic deletions or p53 mutations are important genetic changes in ovarian cancer.
我们研究了19例人类卵巢癌和17例卵巢交界性肿瘤,以确定17号染色体短臂上杂合性缺失情况以及可能同时存在的p53基因突变。采用限制性片段长度多态性研究评估等位基因缺失情况,通过单链构象多态性分析和直接测序检测p53基因突变。此外,我们对相同的肿瘤切片进行免疫组化染色,以检测组织中的p53蛋白。在检测的19例卵巢恶性肿瘤样本中,19例有信息的病例中有12例(63.2%)发现了17p等位基因缺失。19例恶性卵巢肿瘤中有7例(36.8%)观察到p53基因突变,且主要在17p等位基因缺失的肿瘤中观察到(7例中有6例,85.7%)。虽然17例卵巢交界性肿瘤中有9例在单链构象多态性分析中显示条带迁移,但直接测序仅证实1例存在点突变。我们还在19例卵巢癌中获得6例(31.6%)免疫反应阳性病例,在17例卵巢交界性肿瘤中获得3例(17.6%)。我们得出结论,17p等位基因缺失或p53基因突变导致的肿瘤抑制基因功能丧失或失活是卵巢癌重要的基因改变。