Integrated Analysis of Copy Number Variation and Genome-Wide Expression Profiling in Colorectal Cancer Tissues

Abstract

Integrative analyses of multiple genomic datasets for selected samples can provide better insight into the overall data and can enhance our knowledge of cancer. The objective of this study was to elucidate the association between copy number variation (CNV) and gene expression in colorectal cancer (CRC) samples and their corresponding non-cancerous tissues. Sixty-four paired CRC samples from the same patients were subjected to CNV profiling using the Illumina HumanOmni1-Quad assay, and validation was performed using multiplex ligation probe amplification method. Genome-wide expression profiling was performed on 15 paired samples from the same group of patients using the Affymetrix Human Gene 1.0 ST array. Significant genes obtained from both array results were then overlapped. To identify molecular pathways, the data were mapped to the KEGG database. Whole genome CNV analysis that compared primary tumor and non-cancerous epithelium revealed gains in 1638 genes and losses in 36 genes. Significant gains were mostly found in chromosome 20 at position 20q12 with a frequency of 45.31% in tumor samples. Examples of genes that were associated at this cytoband were PTPRT, EMILIN3 and CHD6. The highest number of losses was detected at chromosome 8, position 8p23.2 with 17.19% occurrence in all tumor samples. Among the genes found at this cytoband were CSMD1 and DLC1. Genome-wide expression profiling showed 709 genes to be up-regulated and 699 genes to be down-regulated in CRC compared to non-cancerous samples. Integration of these two datasets identified 56 overlapping genes, which were located in chromosomes 8, 20 and 22. MLPA confirmed that the CRC samples had the highest gains in chromosome 20 compared to the reference samples. Interpretation of the CNV data in the context of the transcriptome via integrative analyses may provide more in-depth knowledge of the genomic landscape of CRC.

Integrative Analysis of DNA Methylation and Gene Expression Identify a Three-Gene Signature for Predicting Prognosis in Lower-Grade Gliomas

“…Previous study using whole genome copy number variation (CNV) analysis revealed that the EMILIN3 gene was significantly increased in copy number in colorectal cancer samples as compared to non-cancerous samples [37]. However, the role of EMILIN3 in gliomas remains unclear.…”

Influenza Virus and Chromatin: Role of the CHD1 Chromatin Remodeler in the Virus Life Cycle

“…CHD6 is found at intranuclear sites of mRNA synthesis (43) and operates as a coactivator for the cellular Nrf2 transcription factor (61). Very little is known of CHD6 function, although reports suggest its involvement in processes such as human cancers (62)(63)(64). Mutations in the CHD7 gene are described as responsible for CHARGE syndrome, a complex neurological syndrome (65); since it interacts with CHD7, CHD8 might also be involved in CHARGE syndrome (66).…”

Utilization of the oncoscan microarray assay in cancer diagnostics

“…Gene expression profiling could identify involved genes within large gain regions; however, there could be discrepancies between the degree of structural variation and gene expression levels [1,26,27]. Gene expression profiling has discovered novel cancer genes whose induction mechanisms are independent of CNVs [27].…”