Tuhkanen Hanna, Anttila Maarit, Kosma Veli-Matti, Heinonen Seppo, Juhola Matti, Helisalmi Seppo, Kataja Vesa, Mannermaa Arto
Department of Pathology and Forensic Medicine, University of Kuopio and Kuopio University Hospital, Kuopio, Finland.
Int J Cancer. 2006 Sep 15;119(6):1345-53. doi: 10.1002/ijc.21785.
Stromal cells are an active and integral part of epithelial neoplasms. We have previously observed allelic imbalance on chromosome 3p21 in both stromal and epithelial cells of ovarian tumors. This study was designed to explore gene dosage alterations throughout human chromosomes from stromal and epithelial cells of epithelial ovarian carcinomas. Thirteen stromal and 24 epithelial samples, microdissected from epithelial ovarian carcinomas, were analyzed using multiplex ligation-dependent probe amplification technique. Analysis covered 110 cancer related genes. Frequent genetic alterations were detected both in the stroma and epithelium of ovarian carcinomas. The mean number of altered genes per tumor was 10.8 in stroma and 23.6 in epithelium. In the stroma, the mean number of gains was 6.6 and of losses 4.2 and in the epithelium 13.7 and 9.9. The high number of changes associated with advanced tumor stage (p = 0.035) and death due to ovarian cancer (p = 0.032). The most frequent alteration was the deletion of the deleted in colorectal carcinoma (DCC) on chromosome 18q21.3 in 62% of samples. Loss of DCC was related to endometrioid subtype (p = 0.033). Large chromosomal aberrations were detected on the basis of alterations in adjacent genes. Most importantly, 38 genes showed similar genetic alterations (gain-gain or loss-loss) in stromal and epithelial compartments of 11 tumor pairs. Thus, frequent genetic alterations in stromal cells of epithelial ovarian carcinomas resembled those of malignant epithelial cells and may indicate a common precursor cell type. Epithelial-mesenchymal transition may generate transformed cancer cells and modify the tumor microenvironment with distinct properties.
基质细胞是上皮性肿瘤中活跃且不可或缺的一部分。我们之前在卵巢肿瘤的基质细胞和上皮细胞中均观察到3号染色体短臂21区的等位基因失衡。本研究旨在探索上皮性卵巢癌的基质细胞和上皮细胞中整个人类染色体上的基因剂量改变。使用多重连接依赖探针扩增技术对从上皮性卵巢癌中显微切割得到的13个基质样本和24个上皮样本进行分析。分析涵盖了110个癌症相关基因。在卵巢癌的基质和上皮中均检测到频繁的基因改变。每个肿瘤中改变基因的平均数量在基质中为10.8个，在上皮中为23.6个。在基质中，获得的平均数量为6.6个，缺失的平均数量为4.2个；在上皮中，获得的平均数量为13.7个，缺失的平均数量为9.9个。改变的数量与肿瘤晚期（p = 0.035）以及卵巢癌导致的死亡（p = 0.032）相关。最常见的改变是18号染色体长臂21.3区的结直肠癌缺失基因（DCC）在62%的样本中发生缺失。DCC的缺失与子宫内膜样亚型相关（p = 0.033）。基于相邻基因的改变检测到了大的染色体畸变。最重要的是，在11对肿瘤的基质和上皮区域中，有38个基因显示出相似的基因改变（获得-获得或缺失-缺失）。因此，上皮性卵巢癌基质细胞中频繁的基因改变类似于恶性上皮细胞的改变，可能表明存在一种共同的前体细胞类型。上皮-间质转化可能产生转化的癌细胞并改变具有独特特性的肿瘤微环境。
