Comparison of serous and mucinous ovarian carcinomas: Distinct pattern of allelic loss at distal 8p and expression of transcription factor GATA-4
Comparison of serous and mucinous ovarian carcinomas: Distinct pattern of allelic loss at distal 8p and expression of transcription factor GATA-4
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DOI：
10.1038/labinvest.3780260
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发表时间：
2001-04-01
影响因子：
5
通讯作者：
Butzow, R
中科院分区：
文献类型：
--
作者：
Lassus, H;Laitinen, MPE;Butzow, R
利用比较基因组杂交技术(CGH)，我们已经证实8P在卵巢癌中频繁丢失，尤其是其远端部分。为了比较浆液性和粘液性卵巢癌远端8p基因缺失图谱，我们对位于8p21-p23的18个多态微卫星标记进行了等位基因分析。在浆液性癌中。杂合性缺失(LOH)在67%的样本中被检测到，大多数癌症表现出全部或大部分信息性标记的丢失。相比之下，只有21%的粘液性癌表现出等位基因缺失，每个样本中只有一个或两个座位显示杂合性缺失。在浆液性癌中，LOH与较高级别的肿瘤相关。在浆液性癌中可以定义三个不同的最小共同缺失区(8p21.1、8p22-p23.1和8p23.1)。应用Northern印迹和免疫组织化学肿瘤芯片技术，研究了位于其中一个区域(8p23.1)的转录因子基因GATA4在浆液性和粘液性卵巢癌中的表达。发现在大多数浆液性癌中表达缺失，但在大多数粘液性癌中仍有表达。我们的结果提示在浆液性和粘液性卵巢癌中存在不同的致病途径，并且在8p处存在多于一个的肿瘤抑制基因参与了浆液性癌的发生。
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.