Correction: Novel Genes Associated with Colorectal Cancer Are Revealed by High Resolution Cytogenetic Analysis in a Patient Specific Manner

Abstract

Genomic abnormalities leading to colorectal cancer (CRC) include somatic events causing copy number aberrations (CNAs) as well as copy neutral manifestations such as loss of heterozygosity (LOH) and uniparental disomy (UPD). We studied the causal effect of these events by analyzing high resolution cytogenetic microarray data of 15 tumor-normal paired samples. We detected 144 genes affected by CNAs. A subset of 91 genes are known to be CRC related yet high GISTIC scores indicate 24 genes on chromosomes 7, 8, 18 and 20 to be strongly relevant. Combining GISTIC ranking with functional analyses and degree of loss/gain we identify three genes in regions of significant loss (ATP8B1, NARS, and ATP5A1) and eight in regions of gain (CTCFL, SPO11, ZNF217, PLEKHA8, HOXA3, GPNMB, IGF2BP3 and PCAT1) as novel in their association with CRC. Pathway and target prediction analysis of CNA affected genes and microRNAs, respectively indicates TGF-b signaling pathway to be involved in causing CRC. Finally, LOH and UPD collectively affected nine cancer related genes. Transcription factor binding sites on regions of .35% copy number loss/gain influenced 16 CRC genes. Our analysis shows patient specific CRC manifestations at the genomic level and that these different events affect individual CRC patients differently.

The Role of the Meiotic Component in Reproduction of B-RAF-Mutated Melanoma: A Review and “Brainstorming” Session

“…The MREII exonuclease creates DNA nicks guiding the SPO11-TOPOVIBL complex to accurately catalyze DSBs along the genome in specific hotspots [133,134]. Aberrant expression of SPO11 has been found in cell lines of melanoma and also lung cancer [135], see Figure 3, acute myeloid leukemia (AML) [136], cutaneous T-cell lymphoma (CTCL) [137] as well as in patient samples of melanoma, [135,138], cervical cancer [135], gastric cancer [138], and CTCL [139]. Although the exact mechanism of SPO11 reactivation in cancer cells remains elusive, it has been shown that in CTCL, it is regulated epigenetically and temporary expressed at the onset of the cell division in G1/S phase transition [139].…”

Alternatively Spliced Isoforms of MUC4 and ADAM12 as Biomarkers for Colorectal Cancer Metastasis

“…From our previous exon profiling study [ 27 ], we selected MUC4 and ADAM12 for further analysis, as they had the highest, most significant exon-level expression changes. In patients with CRC, alterations of these two genes were reported at multiple levels, including the cytogenetic, gene expression and splicing levels [ 27 , 28 ]. In the present work, we assessed the prognostic significance of these two genes in CRC using The Cancer Genome Atlas (TCGA) database, which was preceded by confirming their differential expression in our patient cohort.…”

Anandamide-Modulated Changes in Metabolism, Glycosylation Profile and Migration of Metastatic Melanoma Cells

“…We observed a significant reduction in both GFAT-1 and DPM1 expressions in metastatic melanoma cells treated with anandamide, which may suggest that the biosynthesis of glycans in these cells was downregulated. As shown in the literature, GFAT-1 and DPM1 overexpression is of a cell/patient specific manner [62], but the activity of the enzymes encoded by the investigated genes may also be influenced by several genetic and metabolic alterations [63]. During the epithelial-to-mesenchymal transition (EMT) of A549 lung cancer cells, the glucose uptake was intensified, but instead of increasing the glycolysis, the glucose was directed to the HBP pathway [64].…”

“…Altered DPMs gene expression level and enzyme activity (the only known mannose donor for mannosylation in the lumen of the endoplasmic reticulum) in humans is linked to cancer and congenital disorders of glycosylation [67,68]. The DPM1 gene plays a crucial role in colorectal cancer [62] and breast cancer, but its expression measured by means of the microarray analysis in tissue samples obtained from patients with breast cancer showed significant differences in values ranging from 761 up to even 5424 [69]. Considering this information, the obtained result confirmed the cell-dependent differences in the overexpression of the investigated genes.…”