Positive Caricature Transcriptomic Effects Associated with Broad Genomic Aberrations in Colorectal Cancer

被引：16

作者：

Condorelli, Daniele F. ^{[1
]}

Spampinato, Giorgia ^{[1
]}

Valenti, Giovanna ^{[1
]}

Musso, Nicolo ^{[1
]}

Castorina, Sergio ^{[2
]}

Barresi, Vincenza ^{[1
]}

机构：

[1] Univ Catania, Sect Med Biochem, Dept Biomed & Biotechnol Sci, I-95123 Catania, Italy

[2] Univ Catania, Dept Med & Surg Sci & Adv Technol, I-95123 Catania, Italy

来源：

SCIENTIFIC REPORTS | 2018年 / 8卷

关键词：

COPY-NUMBER ALTERATIONS; ACUTE MYELOID-LEUKEMIA; ABERRANT CHROMOSOMAL REGIONS; ACQUIRED UNIPARENTAL DISOMY; GENE-EXPRESSION; NEUTRAL-LOSS; PROGNOSTIC MARKER; POOR-PROGNOSIS; HETEROZYGOSITY; PROGRESSION;

D O I：

10.1038/s41598-018-32884-3

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：16

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