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Induced Chromosomal Aneuploidy Results in Global and Consistent Deregulation of the Transcriptome of Cancer Cells.
- Source :
-
Neoplasia (New York, N.Y.) [Neoplasia] 2019 Jul; Vol. 21 (7), pp. 721-729. Date of Electronic Publication: 2019 Jun 04. - Publication Year :
- 2019
-
Abstract
- 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.<br /> (Copyright © 2019. Published by Elsevier Inc.)
- Subjects :
- Aneuploidy
Colorectal Neoplasms pathology
Comparative Genomic Hybridization
DNA Copy Number Variations genetics
Gene Expression Regulation, Neoplastic
Humans
Neoplasm Proteins genetics
Transcriptional Activation genetics
Chromosomes genetics
Colorectal Neoplasms genetics
Monomeric GTP-Binding Proteins genetics
Transcriptome genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1476-5586
- Volume :
- 21
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Neoplasia (New York, N.Y.)
- Publication Type :
- Academic Journal
- Accession number :
- 31174021
- Full Text :
- https://doi.org/10.1016/j.neo.2019.04.009