artificially introduced aneuploid chromosomes assume a conserved position in colon cancer cells人为地引入了非整倍体染色体假设在结肠癌细胞保存位置.pdf

Artificially Introduced Aneuploid Chromosomes Assume a Conserved Position in Colon Cancer Cells 1 1 1 1 2¤ 2 Kundan Sengupta , Madhvi B. Upender , Linda Barenboim-Stapleton , Quang Tri Nguyen , Stephen M. Wincovitch Sr. , Susan H. Garfield , 1 1 Michael J. Difilippantonio , Thomas Ried * 1 Genetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America, 2 Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America Background. Chromosomal 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 Findings. We 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. Conclusions. Our data is therefore consistent