Lassus H, Laitinen M P, Anttonen M, Heikinheimo M, Aaltonen L A, Ritvos O, Butzow R
Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Helsinki, Finland.
Lab Invest. 2001 Apr;81(4):517-26. doi: 10.1038/labinvest.3780260.
Using comparative genomic hybridization (CGH), we have previously demonstrated frequent loss of 8p, especially its distal part, in ovarian carcinoma. To compare the deletion map of distal 8p in serous and mucinous ovarian carcinomas, we performed allelic analysis with 18 polymorphic microsatellite markers at 8p21-p23. In serous carcinoma, loss of heterozygosity (LOH) was detected in 67% of the samples, and the majority of the carcinomas showed loss of all or most of the informative markers. In contrast, only 21% of mucinous carcinomas showed allelic loss, with only one or two loci showing LOH in each sample. In serous carcinomas, LOH was associated with higher grade tumors. Three distinct minimal common regions of loss could be defined in serous carcinomas (at 8p21.1, 8p22-p23.1, and 8p23.1). Expression of a transcription factor gene, GATA4, located at one of these regions (8p23.1) was studied in serous and mucinous ovarian carcinomas by Northern blotting and immunohistochemical staining of tumor microarray. Expression was found to be lost in most serous carcinomas but retained in the majority of mucinous carcinomas. Our results suggest distinct pathogenetic pathways in serous and mucinous ovarian carcinomas and the presence of more than one tumor suppressor gene at 8p involved in the tumorigenesis of serous carcinoma.
我们先前运用比较基因组杂交（CGH）技术，证实在卵巢癌中8p尤其是其远端部分经常缺失。为比较浆液性和黏液性卵巢癌中8p远端的缺失图谱，我们使用位于8p21 - p23的18个多态性微卫星标记进行等位基因分析。在浆液性癌中，67%的样本检测到杂合性缺失（LOH），并且大多数癌显示所有或大部分信息性标记缺失。相比之下，只有21%的黏液性癌显示等位基因缺失，每个样本仅有一两个位点显示LOH。在浆液性癌中，LOH与高分级肿瘤相关。在浆液性癌中可确定三个不同的最小共同缺失区域（位于8p21.1、8p22 - p23.1和8p23.1）。通过对肿瘤微阵列进行Northern印迹和免疫组织化学染色，研究了位于这些区域之一（8p23.1）的转录因子基因GATA4在浆液性和黏液性卵巢癌中的表达。发现大多数浆液性癌中该基因表达缺失，但在大多数黏液性癌中表达保留。我们的结果提示浆液性和黏液性卵巢癌存在不同的发病机制途径，并且8p上存在不止一个肿瘤抑制基因参与浆液性癌的肿瘤发生。
