%0 Journal Article
%T Induced Chromosomal Aneuploidy Results in Global and Consistent Deregulation of the Transcriptome of Cancer Cells
%A Amanda B. Hummon
%A Christina H. Stuelten
%A Darawalee Wangsa
%A Georg Emons
%A Howard H. Yang
%A Jordi Camps
%A Kerry M. Bauer
%A Leigh A. Weston
%A Lidia Warner
%A Madhvi Upender
%A Maria Vila-Casades¨²s
%A Markus Brown
%A Maxwell P. Lee
%A Philip Brauer
%A R¨¹diger Braun
%A Thomas Ried
%A Yue Hu
%J Archive of "Neoplasia (New York, N.Y.)".
%D 2019
%R 10.1016/j.neo.2019.04.009
%X Chromosomal aneuploidy is a defining feature of epithelial cancers. The pattern of aneuploidies is cancer-type specific. For instance, the gain of chromosome 13 occurs almost exclusively in colorectal cancer. We used microcell-mediated chromosome transfer to generate gains of chromosome 13 in the diploid human colorectal cancer cell line DLD-1. Extra copies of chromosome 13 resulted in a significant and reproducible up-regulation of transcript levels of genes on chromosome 13 (P£¿=£¿.0004, FDR£¿=£¿0.01) and a genome-wide transcriptional deregulation in all 8 independent clones generated. Genes contained in two clusters were particularly affected: the first cluster on cytoband 13q13 contained 7 highly up-regulated genes (NBEA, MAB21L1, DCLK1, SOHLH2, CCDC169, SPG20 and CCNA1, P£¿=£¿.0003) in all clones. A second cluster was located on 13q32.1 and contained five upregulated genes (ABCC4, CLDN10, DZIP1, DNAJC3 and UGGT2, P£¿=£¿.003). One gene, RASL11A, localized on chromosome band 13q12.2, escaped the copy number-induced overexpression and was reproducibly and significantly down-regulated on the mRNA and protein level (P£¿=£¿.0001, FDR£¿=£¿0.002). RASL11A expression levels were also lower in primary colorectal tumors as compared to matched normal mucosa (P£¿=£¿.0001, FDR£¿=£¿0.0001. Overexpression of RASL11A increases cell proliferation and anchorage independent growth while decreasing cell migration in +13 clones. In summary, we observed a strict correlation of genomic copy number and resident gene expression levels, and aneuploidy dependent consistent genome-wide transcriptional deregulation
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6551473/