Structural alteration of chromosomes and transcription activity in human cancer cells

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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.