Structural alteration of chromosomes and transcription activity in human cancer cells

染色体区域（CT）是间期细胞中单个染色体所占据的核内亚区域，亚染色体定位（SCP）是间期细胞核中基因的染色体内或染色体外定位。我们用荧光原位杂交方法研究了正常甲状腺组织（NT）、腺瘤性甲状腺肿（AG）、乳头状癌（PC）和未分化癌（UC）上皮细胞中染色体10（CS10）、18（CS18）和19（CS19）的CT。CS 10和CS 18的放射状定位分别在超过60%和80%的细胞中检测到在核的周边，而CS 19的放射状定位在超过80%的细胞中的核的中心区域。在PC中，CS 10和CS 18的径向定位模式与NT相似。与NT细胞相比，PC中具有中央定位的CS 19的核较少见。另一方面，具有DNA扩增的细胞的UC显示CS 10、CS 18和CS 19径向位置的位置异常。此外，我们研究了表皮分化复合物（EDC）基因在染色体1（CS1）的非肿瘤性鳞状细胞和柱状细胞鳞状化生或不鳞状化生的SCP。化生细胞的SCP与鳞状细胞相似，与柱状细胞和淋巴细胞相似。最后，我们研究了尿路上皮癌细胞染色体异常与核形态的关系。高级别尿路上皮癌患者的尿路上皮细胞染色体异常较低级别尿路上皮癌多见，核型异常严重。根据这些结果，我们认为染色体的高维结构如CT和SCP的改变可能影响癌细胞和非肿瘤细胞的癌变、RNA转录、基因表达和形态发生。

Chromosome territories (CTs) are intranuclear subregions occupied by individual chromosomes in an interphase cell, and subchromosomal positioning (SCP) is intra- or extra-chromosomal location of genes in the interphase nucleus. We investigated CTs of chromosomes 10 (CS10), 18 (CS18), and 19 (CS19)in epithelial cells from normal thyroid tissue (NT), adenomatous goiters (AGs), papillary carcinomas (PCs), and undifferentiated carcinomas (UCs) using the multicolor fluorescence in situ hybridization method In the NT and AGs, the radial positionings of CS10 and CS 18 were detected at the periphery of nuclei in more than 60% and 80% of cells, respectively, whereas the radial positioning of CS19 was in the central region of the nuclei in more than 80% of cells. In the PCs, radial positioning pattern of CS10 and CS18 were similar to that in the NT. The nuclei with centrally located CS19 in PCs were less frequent than those in NT cells. On the other hand, UCs with cells having DNA amplification demonstrated the locational abnormalities of the CS 10, CS 18, and CS19 radial positions. Also, we studied SCP of Epidermal differentiation complex (EDC) gene in chromosome 1 (CS1) in non-neoplastic squamous and columnar cells with or without squamous metaplasia. SCP of metaplastic cells was similar with squamous cells compared with columnar cells as well as lymphocytes. Finally we investigated the relation between chromosomal abnormalities and nuclear morphology in urothelial carcinoma cells. The urothelial cells of high grade urothelial carcinoma cases indicated more frequent and various chromosomal abnormalities with severe nuclear atypia than those of low grade urothelial carcinoma. Based on these results, we concluded that alteration of high dimensional structure of chromosomes such as CT and SCP may affect the carcinogenesis, RNA transcription, gene expression and morphogenesis in carcinoma cells as well as non neoplastic cells.