Structural alteration of chromosomes and transcription activity in human cancer cells

染色体区域（CTs）是间期细胞中单个染色体占据的核内亚区，而亚染色体定位（SCP）是间期细胞核中基因的染色体内或染色体外定位。采用多色荧光原位杂交技术对正常甲状腺组织（NT）、腺瘤性甲状腺肿大（AGs）、乳头状癌（PCs）和未分化癌（UCs）上皮细胞中10号染色体（CS10）、18号染色体（CS18）和19号染色体（CS19）的ct进行了检测。在NT和AGs中，分别有超过60%和80%的细胞在细胞核外周检测到CS10和CS18的径向定位。而CS19在80%以上的细胞中径向定位在细胞核的中心区域。在PCs中，CS10和CS18的径向定位模式与NT相似，在PCs中，CS19位于中心的细胞核比NT中少。另一方面，具有DNA扩增细胞的UCs显示cs10， cs18和CS19径向位置异常。此外，我们还研究了非肿瘤性鳞状和柱状细胞伴或不伴鳞状化生的1号染色体表皮分化复合体（EDC）基因的SCP。化生细胞的SCP与鳞状细胞、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细胞核形态的关系。高级别尿路上皮癌患者的尿路上皮细胞比低级别尿路上皮癌患者表现出更频繁、更多样的染色体异常和严重的核异型性。基于这些结果，我们认为CT和SCP等染色体高维结构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.