1. Positive Caricature Transcriptomic Effects Associated with Broad Genomic Aberrations in Colorectal Cancer
- Author
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Sergio Castorina, Vincenza Barresi, Nicolò Musso, Daniele F. Condorelli, Giovanna Valenti, and Giorgia Spampinato
- Subjects
0301 basic medicine ,DNA Copy Number Variations ,Colorectal cancer ,Normal tissue ,Loss of Heterozygosity ,lcsh:Medicine ,Biology ,Gene dosage ,Article ,Transcriptome ,03 medical and health sciences ,Downregulation and upregulation ,medicine ,Chromosomes, Human ,Humans ,RNA, Messenger ,lcsh:Science ,Gene ,Genetics ,Multidisciplinary ,Genome, Human ,Gene Expression Profiling ,lcsh:R ,Cancer ,medicine.disease ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,lcsh:Q ,Colorectal Neoplasms - Abstract
We re-examined the correlation between Broad Genomic Aberrations (BGAs) and transcriptomic profiles in Colorectal Cancer (CRC). Two types of BGAs have been examined: Broad Copy-Number Abnormal regions (BCNAs), distinguished in gain- and loss-type, and Copy-Neutral Loss of Heterozygosities (CNLOHs). Transcripts are classified as “OverT” or “UnderT” if overexpressed or underexpressed comparing CRCs bearing a specific BGA to CRCs not bearing it and as “UpT” or “DownT” if upregulated or downregulated in cancer compared to normal tissue. BGA-associated effects were evaluated by changes in the “Chromosomal Distribution Index” (CDI) of different transcript classes. Data show that UpT are more sensitive than DownT to BCNA-associated gene dosage effects. “Over-UpT” genes are upregulated in cancer and further overexpressed by gene dosage, defining the so called “positive caricature transcriptomic effect”. When Over-UpT genes are ranked according to overexpression, top positions are occupied by genes implicated at the functional and therapeutic level in CRC. We show that cancer-upregulated transcripts are sensitive markers of BCNA-induced effects and suggest that analysis of positive caricature transcriptomic effects can provide clues toward the identification of BCNA-associated cancer driver genes.
- Published
- 2018
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