Copy number variations are progressively associated with the pathogenesis of colorectal cancer in ulcerative colitis

AIM: To evaluate the association of known copy number variations(CNVs) in ulcerative colitis(UC) progressing to colorectal cancer.METHODS: Microsatellite instability analysis using the National Cancer Institute's panel of markers, and CNV association studies using Agilent 2 × 105 k arrays were done in tissue samples from four patient groups with UC: those at low risk(LR) or high risk of developing colorectal cancer, those with premalignant dysplastic lesions, and those with colitis-associated colorectal cancer(CAC). DNA from tissue samples of these groups were independently hybridized on arrays and analyzed. The data obtained were further subjected to downstream bioinformatics enrichment analysis to examine the correlation with CAC progression.RESULTS: Microarray analysis highlighted a progressive increase in the total number of CNVs [LR(n = 178) vs CAC(n = 958), 5.3-fold], gains and losses [LR(n = 37 and 141) vs CAC(n = 495 and 463), 13.4- and 3.3-fold, respectively], size [LR(964.2 kb) vs CAC(10540 kb), 10.9-fold] and the number of genes in such regions [LR(n = 119) vs CAC(n = 455), 3.8-fold]. Chromosomewise analysis of CNVs also showed an increase in the number of CNVs across each chromosome. There were 38 genes common to all four groups in the study; 13 of these were common to cancer genes from the Genetic Disease Association dataset. The gene set enrichment analysis and ontology analysis highlighted many cancerassociated genes. All the samples in the different groupswere microsatellite stable.CONCLUSION: Increasing numbers of CNVs are associated with the progression of UC to CAC, and warrant further detailed exploration.

Deregulated miRNA clusters in ovarian cancer:Imperative implications in personalized medicine

Ovarian cancer(OC)is one of the most common and fatal types of gynecological cancer.OC is usually detected at the advanced stages of the disease,making it highly lethal.miRNAs are single-stranded,small non-coding RNAs with an approximate size ranging around 22 nt.Interestingly,a considerable proportion of miRNAs are organized in clusters with miRNA genes placed adjacent to one another,getting transcribed together to result in miRNA clusters(MCs).MCs comprise two or more miRNAs that follow the same orientation during transcription.Abnormal expression of the miRNA cluster has been identified as one of the key drivers in OC.MC exists both as tumor-suppressive and oncogenic clusters and has a significant role in OC pathogenesis by facilitating cancer cells to acquire various hallmarks.The present review summarizes the regulation and biological function of MCs in OC.The review also highlights the utility of abnormally expressed MCs in the clinical management of OC.