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Chromosomal Density of Cancer Up-Regulated Genes, Aberrant Enhancer Activity and Cancer Fitness Genes Are Associated with Transcriptional Cis-Effects of Broad Copy Number Gains in Colorectal Cancer.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2019 Sep 19; Vol. 20 (18). Date of Electronic Publication: 2019 Sep 19. - Publication Year :
- 2019
-
Abstract
- Broad Copy Number Gains (BCNGs) are copy-number increases of chromosomes or large segments of chromosomal arms. Publicly-available single-nucleotide polymorphism (SNP) array and RNA-Seq data of colon adenocarcinoma (COAD) samples from The Cancer Genome Atlas (TCGA) consortium allowed us to design better control groups in order to identify changes in expression due to highly recurrent BCNGs (in chromosomes 20, 8, 7, 13). We identified: (1) Overexpressed Transcripts ( OverT ), transcripts whose expression increases in "COAD groups bearing a specific BCNG" in comparison to "control COAD groups" not bearing it, and (2) up-regulated/down-regulated transcripts , transcripts whose expression increases/decreases in COAD groups in comparison to normal colon tissue. An analysis of gene expression reveals a correlation between the density of up-regulated genes per selected chromosome and the recurrence rate of their BCNGs. We report an enrichment of gained enhancer activity and of cancer fitness genes among OverT genes. These results support the hypothesis that the chromosomal density of overexpressed cancer fitness genes might play a significant role in the selection of gained chromosomes during cancer evolution. Analysis of functional pathways associated with OverT suggest that some multi-subunit protein complexes (eIF2, eIF3, CSTF and CPSF) are candidate targets for silencing transcriptional therapy.
- Subjects :
- Chromosomes, Human genetics
Humans
Adenocarcinoma genetics
Adenocarcinoma metabolism
Adenocarcinoma pathology
Chromosomes, Human metabolism
Colonic Neoplasms genetics
Colonic Neoplasms metabolism
Colonic Neoplasms pathology
Enhancer Elements, Genetic
Gene Dosage
Gene Expression Regulation, Neoplastic
Genes, Neoplasm
Models, Biological
Neoplasm Proteins biosynthesis
Neoplasm Proteins genetics
Up-Regulation
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 20
- Issue :
- 18
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 31546890
- Full Text :
- https://doi.org/10.3390/ijms20184652