Landscape of transcriptome variations uncovering known and novel driver events in colorectal carcinoma

Abstract

We focused on an integrated view of genomic changes in Colorectal cancer (CRC) and distant normal colon tissue (NTC) to test the effectiveness of expression profiling on identification of molecular targets. We performed transcriptome on 16 primary coupled CRC and NTC tissues. We identified pathways and networks related to pathophysiology of CRC and selected potential therapeutic targets. CRC cells have multiple ways to reprogram its transcriptome: a functional enrichment analysis in 285 genes, 25% mutated, showed that they control the major cellular processes known to promote tumorigenesis. Among the genes showing alternative splicing, cell cycle related genes were upregulated (CCND1, CDC25B, MCM2, MCM3), while genes involved in fatty acid metabolism (ACAAA2, ACADS, ACAT1, ACOX, CPT1A, HMGCS2) were downregulated. Overall 148 genes showed differential splicing identifying 17 new isoforms. Most of them are involved in the pathogenesis of CRC, although the functions of these variants remain unknown. We identified 2 in-frame fusion events, KRT19-KRT18 and EEF1A1-HSP90AB1, encoding for chemical proteins in two CRC patients. We draw a functional interactome map involving integrated multiple genomic features in CRC. Finally, we underline that two functional cell programs are prevalently deregulated and absolutely crucial to determinate and sustain CRC phenotype.

Pediatric fibromyxoid soft tissue tumor with PLAG1 fusion: A novel entity?

“…Gene fusions involving EEF1A1 have only been rarely reported. In all cases, EEF1A1 was the 5′ partner, fused to HSP90AB1 in two cases of colonic adenocarcinoma, 10 PDL2 in one case of diffuse large B cell lymphoma in an 18‐year‐old male, 12 and RPL32 in a case of CIC‐DUX4 sarcoma in an 11‐year‐old male. In the last case, the fusion was only found in the post‐treatment specimen, not the initial biopsy 11 .…”

Distant Metastasis in Colorectal Cancer Patients—Do We Have New Predicting Clinicopathological and Molecular Biomarkers? A Comprehensive Review

“…Gene expression profiling of cancer cells has been used for decade to accurately classify tumors and to identify markers predicting the patient’s outcome. In the case of primary CRC tumors, numerous expression studies have been conducted so far [ 124 , 125 , 126 ].…”

Integrated Analysis of miRNA and mRNA Endorses a Twenty miRNAs Signature for Colorectal Carcinoma

“…The comparison of differentially expressed (DE) miRNAs with whole-transcriptome profiles of CRC and NCT [11] allowed us to identify a set of 21 miRNAs enriched in anti-expressed targets (Table S1: List of 21 deregulated miRNAs identified by array and gene targets anti-expressed identified by RNA-Seq).…”

“…We identified gene targets for each deregulated miRNA by anti-correlation analysis between the 20 identified miRNAs and RNA-Seq data of 47 CRC and NCT [11]. An enrichment analysis of gene targets controlled by downregulated miRNAs in CRC have brought to light 25 genes known to relate to the pathogenesis of CRC.…”

“…Predicted miRNA targets were then compared with the transcriptional profiles of CRC and NCT samples obtained by Next Generation Sequencing experiments [11], searching for significant overlaps between predicted targets of miRNA and mRNA whose expression was the opposite of that of miRNAs. The mRNAs with inverse expression were defined as anti-expressed.…”