Abstract
BackgroundChromosomal aneuploidy is a defining feature of carcinomas. For instance, in colon cancer, an additional copy of Chromosome 7 is not only observed in early pre-malignant polyps, but is faithfully maintained throughout progression to metastasis. These copy number changes show a positive correlation with average transcript levels of resident genes. An independent line of research has also established that specific chromosomes occupy a well conserved 3D position within the interphase nucleus.Methodology/Principal FindingsWe investigated whether cancer-specific aneuploid chromosomes assume a 3D-position similar to that of its endogenous homologues, which would suggest a possible correlation with transcriptional activity. Using 3D-FISH and confocal laser scanning microscopy, we show that Chromosomes 7, 18, or 19 introduced via microcell-mediated chromosome transfer into the parental diploid colon cancer cell line DLD-1 maintain their conserved position in the interphase nucleus.ConclusionsOur data is therefore consistent with the model that each chromosome has an associated zip code (possibly gene density) that determines its nuclear localization. Whether the nuclear localization determines or is determined by the transcriptional activity of resident genes has yet to be ascertained.
Highlights
Chromosomes assume a non-random and conserved position in the interphase nucleus of higher eukaryotes
This increase was similar upon introduction of Chromosomes 3 and 13 into DLD-1, and was observed when Chromosome 3 was introduced into normal mammary epithelial cells [12]
The systematic exploration of the consequences of chromosomal aneuploidies on gene expression profiles has shown that a direct relationship exists between genomic copy number and transcript levels [8,10,14,15]
Summary
Chromosomes assume a non-random and conserved position in the interphase nucleus of higher eukaryotes. Extensive studies in mice show cell type specific, non-random chromosome arrangements based on both gene density and chromosome size [4]. Together, these data suggest a functional significance of chromosome positioning. Neither the basis for such an arrangement, nor the nature of its structure/function relationship, has yet been revealed It remains to be determined how the nuclear distribution of chromosomes correlates with their transcriptional activity. In colon cancer, an additional copy of Chromosome 7 is observed in early pre-malignant polyps, but is faithfully maintained throughout progression to metastasis These copy number changes show a positive correlation with average transcript levels of resident genes. Whether the nuclear localization determines or is determined by the transcriptional activity of resident genes has yet to be ascertained
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